Delivery devices with coolable energy emitting assemblies

ABSTRACT

Systems, delivery devices, and methods to treat to ablate, damage, or otherwise affect tissue. The treatment systems are capable of delivering a coolable ablation assembly that ablates targeted tissue without damaging non-targeted tissue. The coolable ablation assembly damages nerve tissue to temporarily or permanently decrease nervous system input.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/913,702 filed Oct. 27, 2010, which claims the benefit under 35 U.S.C.§119(e) of U.S. Provisional Patent Application No. 61/255,367 filed Oct.27, 2009 and U.S. Provisional Patent Application No. 61/260,348 filedNov. 11, 2009. Each of these applications is incorporated herein byreference in its entirety.

BACKGROUND

1. Technical Field

The present invention generally relates to systems, apparatuses, andmethods for treating tissue, and more particularly, the inventionrelates to systems or treatment systems with delivery devices havingcoolable energy emitting assemblies for eliciting a desired response.

2. Description of the Related Art

Pulmonary diseases may cause a wide range of problems that adverselyaffect performance of the lungs. Pulmonary diseases, such as asthma andchronic obstructive pulmonary disease (“COPD”), may lead to increasedairflow resistance in the lungs. Mortality, health-related costs, andthe size of the population having adverse effects due to pulmonarydiseases are all substantial. These diseases often adversely affectquality of life. Symptoms are varied but often include cough;breathlessness; and wheeze. In COPD, for example, breathlessness may benoticed when performing somewhat strenuous activities, such as running,jogging, brisk walking, etc. As the disease progresses, breathlessnessmay be noticed when performing non-strenuous activities, such as walkingOver time, symptoms of COPD may occur with less and less effort untilthey are present all of the time, thereby severely limiting a person'sability to accomplish normal tasks.

Pulmonary diseases are often characterized by airway obstructionassociated with blockage of an airway lumen, thickening of an airwaywall, alteration of structures within or around the airway wall, orcombinations thereof. Airway obstruction can significantly decrease theamount of gas exchanged in the lungs resulting in breathlessness.Blockage of an airway lumen can be caused by excessive intraluminalmucus or edema fluid, or both. Thickening of the airway wall may beattributable to excessive contraction of the airway smooth muscle,airway smooth muscle hypertrophy, mucous glands hypertrophy,inflammation, edema, or combinations thereof. Alteration of structuresaround the airway, such as destruction of the lung tissue itself, canlead to a loss of radial traction on the airway wall and subsequentnarrowing of the airway.

Asthma can be characterized by contraction of airway smooth muscle,smooth muscle hypertrophy, excessive mucus production, mucous glandhypertrophy, and/or inflammation and swelling of airways. Theseabnormalities are the result of a complex interplay of localinflammatory cytokines (chemicals released locally by immune cellslocated in or near the airway wall), inhaled irritants (e.g., cold air,smoke, allergens, or other chemicals), systemic hormones (chemicals inthe blood such as the anti-inflammatory cortisol and the stimulantepinephrine), local nervous system input (nerve cells containedcompletely within the airway wall that can produce local reflexstimulation of smooth muscle cells and mucous glands), and the centralnervous system input (nervous system signals from the brain to smoothmuscle cells and mucous glands carried through the vagus nerve). Theseconditions often cause widespread temporary tissue alterations andinitially reversible airflow obstruction that may ultimately lead topermanent tissue alteration and permanent airflow obstruction that makeit difficult for the asthma sufferer to breathe. Asthma can furtherinclude acute episodes or attacks of additional airway narrowing viacontraction of hyper-responsive airway smooth muscle that significantlyincreases airflow resistance. Asthma symptoms include recurrent episodesof breathlessness (e.g., shortness of breath or dyspnea), wheezing,chest tightness, and cough.

Emphysema is a type of COPD often characterized by the alteration oflung tissue surrounding or adjacent to the airways in the lungs.Emphysema can involve destruction of lung tissue (e.g., alveoli tissuesuch as the alveolar sacs) that leads to reduced gas exchange andreduced radial traction applied to the airway wall by the surroundinglung tissue. The destruction of alveoli tissue leaves areas ofemphysematous lung with overly large airspaces that are devoid ofalveolar walls and alveolar capillaries and are thereby ineffective atgas exchange. Air becomes “trapped” in these larger airspaces. This“trapped” air may cause over-inflation of the lung, and in the confinesof the chest restricts the in-flow of oxygen rich air and the properfunction of healthier tissue. This results in significant breathlessnessand may lead to low oxygen levels and high carbon dioxide levels in theblood. This type of lung tissue destruction occurs as part of the normalaging process, even in healthy individuals. Unfortunately, exposure tochemicals or other substances (e.g., tobacco smoke) may significantlyaccelerate the rate of tissue damage or destruction. Breathlessness maybe further increased by airway obstruction. The reduction of radialfraction may cause the airway walls to become “floppy” such that theairway walls partially or fully collapse during exhalation. Anindividual with emphysema may be unable to deliver air out of theirlungs due to this airway collapse and airway obstructions duringexhalation.

Chronic bronchitis is a type of COPD that can be characterized bycontraction of the airway smooth muscle, smooth muscle hypertrophy,excessive mucus production, mucous gland hypertrophy, and inflammationof airway walls. Like asthma, these abnormalities are the result of acomplex interplay of local inflammatory cytokines, inhaled irritants,systemic hormones, local nervous system, and the central nervous system.Unlike asthma where respiratory obstruction may be largely reversible,the airway obstruction in chronic bronchitis is primarily chronic andpermanent. It is often difficult for a chronic bronchitis sufferer tobreathe because of chronic symptoms of shortness of breath, wheezing,and chest tightness, as well as a mucus producing cough.

Different techniques can be used to assess the severity and progressionof pulmonary diseases. For example, pulmonary function tests, exercisecapacity, and quality of life questionnaires are often used to evaluatesubjects. Pulmonary function tests involve objective and reproduciblemeasures of basic physiologic lung parameters, such as total airflow,lung volume, and gas exchange. Indices of pulmonary function tests usedfor the assessment of obstructive pulmonary diseases include the forcedexpiratory volume in 1 second (FEV1), the forced vital capacity (FVC),the ratio of the FEV1 to FVC, the total lung capacity (TLC), airwayresistance and the testing of arterial blood gases. The FEV1 is thevolume of air a patient can exhale during the first second of a forcefulexhalation which starts with the lungs completely filled with air. TheFEV1 is also the average flow that occurs during the first second of aforceful exhalation. This parameter may be used to evaluate anddetermine the presence and impact of any airway obstruction. The FVC isthe total volume of air a patient can exhale during a forcefulexhalation that starts with the lungs completely filled with air. TheFEV1/FVC is the fraction of all the air that can be exhaled during aforceful exhalation during the first second. A FEV1/FVC ratio less than0.7 after the administration of at least one bronchodilator defines thepresence of COPD. The TLC is the total amount of air within the lungswhen the lungs are completely filled and may increase when air becomestrapped within the lungs of patients with obstructive lung disease.Airway resistance is defined as the pressure gradient between thealveoli and the mouth to the rate of air flow between the alveoli andthe mouth. Similarly, resistance of a given airway would be defined asthe ratio of the pressure gradient across the given airway to the flowthrough the airway. Arterial blood gases tests measure the amount ofoxygen and the amount of carbon dioxide in the blood and are the mostdirect method for assessing the ability of the lungs and respiratorysystem to bring oxygen from the air into the blood and to get carbondioxide from the blood out of the body.

Exercise capacity tests are objective and reproducible measures of apatient's ability to perform activities. A six minute walk test (6 MWT)is an exercise capacity test in which a patient walks as far as possibleover a flat surface in 6 minutes. Another exercise capacity testinvolves measuring the maximum exercise capacity of a patient. Forexample, a physician can measure the amount of power the patient canproduce while on a cycle ergometer. The patient can breathe 30 percentoxygen and the work load can increase by 5-10 watts every 3 minutes.

Quality of life questionnaires assess a patient's overall health andwell being. The St. George's Respiratory Questionnaire is a quality oflife questionnaire that includes 75 questions designed to measure theimpact of obstructive lung disease on overall health, daily life, andperceived well-being. The efficacy of a treatment for pulmonary diseasescan be evaluated using pulmonary function tests, exercise capacitytests, and/or questionnaires. A treatment program can be modified basedon the results from these tests and/or questionnaires.

Treatments, such as bronchial thermoplasty, involve destroying smoothmuscle tone by ablating the airway wall in a multitude of bronchialbranches within the lung thereby eliminating both smooth muscles andnerves in the airway walls of the lung. The treated airways are unableto respond favorably to inhaled irritants, systemic hormones, and bothlocal and central nervous system input. Unfortunately, this destructionof smooth muscle tone and nerves in the airway wall may thereforeadversely affect lung performance. For example, inhaled irritants, suchas smoke or other noxious substances, normally stimulate lung irritantreceptors to produce coughing and contracting of airway smooth muscle.Elimination of nerves in the airway walls removes both local nervefunction and central nervous input, thereby eliminating the lung'sability to expel noxious substances with a forceful cough. Eliminationof airway smooth muscle tone may eliminate the airways' ability toconstrict, thereby allowing deeper penetration of unwanted substances,such as noxious substances, into the lung.

Both asthma and COPD are serious diseases with growing numbers ofsufferers. Current management techniques, which include prescriptiondrugs, are neither completely successful nor free from side effects.Additionally, many patients do not comply with their drug prescriptiondosage regiment. Accordingly, it would be desirable to provide atreatment which improves resistance to airflow without the need forpatient compliance.

BRIEF SUMMARY

In some embodiments, a treatment system can be navigated throughairways, such as the right and left main bronchi of the lung root, aswell as more distal airways within the lungs, to treat a wide range ofpulmonary symptoms, conditions, and/or diseases, including, withoutlimitation, asthma, COPD, obstructive lung diseases, or other diseasesthat lead to an increased resistance to airflow in the lungs. Acollapsible ablation assembly can be conveniently passed throughairways. An energy emitter assembly of the ablation assembly can treatone or more target sites without treating non-targeted sites. Even iftargeted anatomical features (e.g., nerves, glands, membranes, and thelike) of main bronchi, lobar bronchi, segmental bronchi or subsegmentalbronchi are treated, non-targeted anatomical features can besubstantially unaltered. For example, the treatment system can destroynerve tissue at target sites without destroying to any significantextent non-targeted tissue that can remain functional after performingtreatment. The energy emitter assembly is coolable to avoid or limitdestruction of non-targeted tissue.

In some embodiments, a system for treating a subject includes a deliverydevice configured to move along a lumen of an airway of a bronchialtree. The delivery device can form lesions to attenuate signalstransmitted by nerve tissue, such as nerve tissue of nerve trunks, whilenot irreversibly damaging to any significant extent non-targetedfeatures, such as an inner surface or smooth muscle of the airway. Thedelivery device can include a distal tip with at least one ablationassembly.

The ablation assembly, in some embodiments, can be moved from alow-profile configuration for delivery to a deployed configuration fortreating tissue at a target region. Ablation elements can be activatedto ablate tissue. Each ablation element can include one or moreelectrodes operable to output ultrasound, electrical energy, and/orradiofrequency (RF) energy. In certain embodiments, each electrode is afluid coolable electrode.

In other embodiments, a delivery device is a catheter with a collapsibleenergy emitter assembly. An expandable element, or other biasingfeature, presses the energy emitter assembly against an airway wall. Theenergy emitter assembly delivers energy to targeted tissue. In certainembodiments, the energy emitter assembly and the expandable element areexpanded simultaneously. In other embodiments, the expandable element isexpanded before or after the energy emitter assembly is deployed.

In some embodiments, a method comprises damaging nerve tissue of a firstmain bronchus to substantially prevent nervous system signals fromtraveling to substantially all distal bronchial branches connected tothe first main bronchus. In some embodiments, most or all of thebronchial branches distal to the first main bronchus are treated. Thedamaged nerve tissue, in certain embodiments, is positioned between atrachea and the lung through which the bronchial branches extend. Themethod can further include damaging nerve tissue of a second mainbronchus to substantially prevent nervous system signals from travelingto substantially all distal bronchial branches connected to the secondmain bronchus.

At least some embodiments can denervate the lung bronchus by creatinglesions using radiofrequency ablation. Ablating nerve trunks whichtraverse along the outside of both the right and left main bronchieffectively disconnects airway smooth muscle which lines the inside ofthe lung airways and mucus producing glands located with the airwaysfrom the vagus nerve and central nervous system. When this occurs,airway smooth muscle relaxes and mucus production is decreased. Thesechanges reduce airway obstruction under states of disease, such as COPDand asthma. Reduced airway obstruction makes breathing easier which canimprove patient quality of life and health status.

The lesions can be shaped or modified using differential temperaturecontrol. Differential temperature control can involve independentcooling of different features of a delivery device, such as an ablationassembly, an expandable element, or an energy emitter assembly.Differential cooling is used to increase or maximize lesion depth. Insome procedures, nerve tissue and other structures (e.g., adjacenttissue structures, organs or diseased tissue such as cancerous ornon-cancerous tumors, etc.) are part of the target region. Additionallyor alternatively, differential cooling can be used to control (e.g.,limit or minimize) or eliminate shallow or surface tissue damage.

Lesions can be formed at target regions. Target regions can include,without limitation, nerve tissue (e.g., tissue of the vagus nerves,nerve trunks, etc.), fibrous tissue, diseased or abnormal tissues (e.g.,cancerous tissue, inflamed tissue, and the like), cardiac tissue, muscletissue, blood, blood vessels, anatomical features (e.g., membranes,glands, cilia, and the like), or other sites of interest. In RFablation, heat is generated due to the tissue resistance as RFelectrical current travels through the tissue. The tissue resistanceresults in power dissipation that is equal to the current flow squaredtimes the tissue resistance. To ablate deep tissues, tissue between anRF electrode and the deep tissue can become heated if active cooling isnot employed. Electrode cooling can be used to keep tissue near theelectrode below a temperature that results in cell death or damage,thereby protecting tissue. For example, cooling can prevent or limitoverheating at the electrode-tissue interface. Overheating (e.g., tissueat temperatures above 95° C. to about 110° C.) can lead to the formationof coagulum, tissue desiccation, tissue charring, and explosiveoutgassing of steam. These effects can result in increased tissueresistance and reduced RF energy transfer into the tissue, therebylimiting the effective RF ablation lesion depth. Active cooling can beused to produce significantly deeper tissue lesions. The temperature ofcoolant for active cooling can be about 0° C. to about 24° C. In someembodiments, the coolant and electrode produce a lesion at a therapeuticdepth of at least about 3 mm. In some embodiments, the lesions can beformed at a depth of about 3 mm to about 5 mm to damage nerve tissue.

Sensors, in some embodiments, are used to monitor temperatures,inflation pressures, coolant flow rates, tissue impedance, or otherparameters of interest. Feedback from the sensors can be used tomodulate the power delivered to electrode(s). Outputted energy can beadjusted to account for local variations in tissue that alters the localimpedance, thus avoiding excess heating which can lead to unwanted hotspots. Lesions can also be formed independent of regional tissuecharacteristics.

In some embodiments, a delivery device comprises an ablation assemblyand a deployable element including a deployable element movable from acollapsed state to an expanded state to bring the tissue-contactingportion of the energy emitter assembly ablation assembly into contactwith tissue, such as an airway wall, cardiac tissue or the like.

The energy emitter assembly, in some embodiments, is configured tooutput energy to ablate targeted tissue of a bronchial tree and throughwhich a coolant is capable of flowing so as to cool a tissue-contactingportion of the energy emitter assembly. A cooling section is configuredto contain the coolant and is movable into contact with the airway wallso as to cool tissue adjacent to the tissue-contacting portion of theenergy emitter assembly when energy is being outputted therefrom. Thedeployable element is configured to contain the coolant such that thecoolant cools the energy emitter assembly and the deployable elementwhen the deployable element is in the expanded state and the ablationassembly is in contact with the airway wall to limit or prevent damageto tissue between the ablation assembly and the targeted tissue. Anelongate shaft is coupled to the ablation assembly and provides coolantflow to the ablation assembly and receives coolant from the ablationassembly.

A controller can be communicatively coupled to a fluid delivery systemand communicatively coupled to a sensor of the ablation assembly. Thecontroller is configured to command the fluid delivery system based onat least one signal from the sensor. The controller is configured toexecute at least one differential cooling program to deliver the firstfluid at a significantly different temperature from the temperature ofthe second fluid. The temperature difference can be at least about 5,10, 20, or 30 degrees C.

In certain embodiments, a delivery device includes an ablation assemblyincluding an energy emitter assembly configured to output energy toablate targeted tissue of a bronchial tree and through which a coolantis capable of flowing so as to cool a tissue-contacting portion of theenergy emitter assembly and a deployable element movable from acollapsed state to an expanded state to bring the tissue-contactingportion of the energy emitter assembly into contact with an airway wallof the bronchial tree. A cooling section is configured to contain thecoolant and movable into contact with the airway wall so as to cooltissue adjacent to the tissue-contacting portion of the energy emitterassembly when energy is being outputted therefrom. An elongate shaft iscoupled to the ablation assembly. Coolant can flow through the shaft tothe ablation assembly.

In some embodiments, a delivery device includes an ablation assemblyincluding an electrode configured to output energy to ablate targetedtissue of an airway. The electrode is movable between a firstorientation in which the electrode extends axially along the airway anda second orientation in which the entire electrode is disposed in aspace between adjacent cartilage rings of the airway.

A delivery device, in some embodiments, includes a deployable elementmovable between a collapsed state and an expanded state. Anintercartilaginous energy emitter assembly surrounds at least a portionof the deployable element. At least a portion of the energy emitterassembly is moveable with respect to the deployable element in theexpanded state to urge an electrode of the energy emitter assemblybetween adjacent cartilage rings of an airway wall of a bronchial tree.

In yet other embodiments, a delivery device includes an ablationassembly including an energy emitter assembly and an inflatable coolingballoon. The energy emitter assembly includes a cooling channel. Theinflatable cooling balloon includes a cooling chamber. An elongate shaftis configured to independently deliver a first fluid to the coolingchannel and a second fluid to the cooling chamber.

A delivery device includes an elongate shaft and ablation assemblycoupled to the elongate shaft. The ablation assembly, in someembodiments, includes an electrode capable of emitting ablation energyand having a first end, a second end, and a main body between the firstend and the second end. At least one of the first end and the second endis covered by an ablation energy insulator, which can be a shield.

A treatment system includes a delivery device configured to deliverenergy to a first tissue surface proximate the delivery device to damagea target region of tissue such that a portion of the target regiondefining a maximum cross-sectional width of the target region isseparated from the first tissue surface.

A method of treating a subject including moves a cooling element of adelivery device through a receiving-opening of an energy emitterassembly located in an airway of the subject. The cooling element isexpanded to position at least a portion of the energy emitter assemblybetween the cooling element and a wall of the airway. Energy isdelivered from the energy emitter assembly to ablate tissue in the wallof the airway while coolant flows through the expanded cooling elementand the energy emitter assembly.

A method of treating a subject includes moving an ablation assembly intoan airway of a bronchial tree. The ablation assembly includes a coolingelement and an energy emitter assembly. The cooling element is expandedto contact a wall of the airway with the cooling element. Energy isdelivered from the energy emitter assembly to damage nerve tissue of anerve trunk extending along the airway. Coolant flows into contact withat least a portion of the energy emitter assembly while delivering theenergy to cool a wall of the airway to limit or prevent cell death intissue located between the damaged nerve tissue and the ablationassembly.

A method of treating a subject includes positioning an ablation assemblyof a delivery device within an airway. Energy is from an electrode ofthe ablation assembly to damage nerve tissue of a nerve trunk such thatnervous system signals transmitted to a portion of the bronchial treeare attenuated. Coolant is delivered through a channel of the electrodeof the ablation assembly.

A method of treating tissue includes delivering energy to the tissuefrom a delivery device positioned near a first surface of the tissue.The energy damages a target region such that a portion of the targetregion defining a maximum cross-sectional width of the target region isseparated from the first surface.

A method of delivering energy includes delivering energy from anelectrode with a substantially uniform voltage across the electrodesurface in contact with the tissue without contacting the tissue withedges of the electrode. The electrode can comprise a plurality ofsub-electrodes that can be independently operated in a desired sequence.

BRIEF DESCRIPTION OF THE DRAWINGS

In the Figures, identical reference numbers identify similar elements oracts.

FIG. 1 is an illustration of lungs, blood vessels, and nerves near toand in the lungs.

FIG. 2 is an illustration of an intraluminal treatment system positionedwithin a left main bronchus according to one embodiment.

FIG. 3 is an illustration of a delivery device extending from a deliveryapparatus positioned in the left main bronchus.

FIG. 4 is a cross-sectional view of an airway of a bronchial tree and apartially expanded ablation assembly positioned along an airway lumen.

FIG. 5 is a cross-sectional view of an airway surrounding the partiallyexpanded ablation assembly when smooth muscle of the airway isconstricted and mucus is in an airway lumen.

FIG. 6 is a graph of the depth of tissue versus the temperature of thetissue.

FIG. 7 is a side elevational view of an ablation assembly in an airway.

FIG. 8 is an isometric view of a delivery device according to oneembodiment.

FIG. 9 is a cross-sectional view of an elongate body taken along a line9-9 of FIG. 8.

FIG. 10 is a front elevational view of the delivery device of FIG. 9.

FIG. 11 is an elevational view of a left side of an ablation assembly.

FIG. 12 is an elevational view of a right side of the ablation assemblyof FIG. 11.

FIG. 13 is a cross-sectional view taken along a line 13-13 of FIG. 11.

FIG. 14 is an isometric view of an electrode assembly.

FIG. 15 is a cross-sectional view of the electrode assembly of FIG. 14taken along a line 15-15.

FIG. 16 is a partial cross-sectional view of a treatment system with adelivery device extending out of a delivery apparatus.

FIG. 17 is a side elevational view of a deployed ablation assembly withfluid flowing through an energy emitter assembly.

FIG. 18 is a cross-sectional view of the deployed ablation assembly withfluid flowing through an expandable member.

FIG. 19 is a cross-sectional view of the ablation assembly with fluidflowing into the expandable member.

FIG. 20 is an elevational view of the ablation assembly with fluidflowing through the energy emitter assembly.

FIG. 21 is a side elevational view of an electrode adjacent acartilaginous ring.

FIG. 22 is a side elevational view of electrodes positioned betweencartilaginous rings.

FIG. 23 is an isometric view of an ablation assembly with a pair ofelectrodes.

FIG. 24 is an isometric view of an ablation assembly with threeelectrodes.

FIG. 25 is a side elevational view of an ablation assembly with adeployed energy emitter assembly and a collapsed expandable element.

FIG. 26 is a side elevational view of the ablation assembly of FIG. 25with the expandable element in an inflated state.

FIG. 27 is a side elevational view of an ablation assembly with acompliant expandable element.

FIG. 28 is a cross-sectional view of the ablation assembly of FIG. 27taken along a line 28-28.

FIG. 29 is a cross-sectional view of the ablation assembly of FIG. 27contacting an airway wall.

FIG. 30 is an isometric view of an ablation assembly with an integralenergy emitter assembly.

FIG. 31 is a cross-sectional view of the ablation assembly taken along aline 31-31.

FIG. 32 is a cross-sectional view of the ablation assembly taken along aline 32-32 of FIG. 31.

FIG. 33 is a side elevational view of a delivery device.

FIG. 34 is a side elevational view of the delivery device of FIG. 33with a deployed expandable element.

FIG. 35 is a cross-sectional view of an elongate body taken along a line35-35 of FIG. 33.

FIG. 36 is a side elevational view of an ablation assembly with inflatedelectrode assemblies.

FIG. 37 is a cross-sectional view of the ablation assemblies of FIG. 36taken along a line 37-37.

FIG. 38 is a detailed view of an electrode assembly of FIG. 37.

FIG. 39 is an isometric view of a multi-component ablation assembly.

FIG. 40 is an isometric view of an expandable element ready to beinserted through a loop of an energy emitter assembly.

FIG. 41 is a side elevational view of the ablation assembly of FIG. 39.

FIG. 42 is a longitudinal cross-sectional view of the ablation assemblyof FIG. 39.

FIG. 43 is an isometric view of an ablation assembly during exhalation.

FIG. 44 is an isometric view of the ablation assembly of FIG. 43 duringinhalation.

FIG. 45 is a top plan view of the ablation assembly of FIG. 43.

FIG. 46 is an isometric view of a coiled ablation assembly.

FIG. 47 is an isometric view of a coiled ablation assembly with anenlarged coil.

FIG. 48 is an isometric view of an ablation assembly with an opencooling channel.

FIG. 49 is a cross-sectional view of the ablation assembly of FIG. 48taken along a line 49-49.

FIG. 50 is a longitudinal cross-sectional view of an ablation assemblyin accordance with another embodiment.

FIG. 51 is a longitudinal cross-sectional view of an ablation assemblywith an actuatable delivery conduit.

FIG. 52 is a cross-sectional view of the ablation assembly of FIG. 51 ina deployed configuration.

FIG. 53 is a cross-sectional view of a portion of the ablation assemblyof FIG. 52 taken along a line 53-53.

FIG. 54 is a transverse cross-sectional view of an energy emitterassembly.

FIG. 55 is a cross-sectional view of the energy emitter assembly of FIG.54 taken along a line 55-55.

FIG. 56 is a transverse cross-sectional view of an energy emitterassembly with a multi-lumen electrode.

FIG. 57 is a cross-sectional view of the energy emitter assembly of FIG.56 taken along a line 57-57.

FIGS. 58 and 59 are cross-sectional views of an electrode contactingtissue.

FIGS. 60 and 61 are cross-sectional views of an electrode with athermally conductive portion contacting tissue.

FIGS. 62 and 63 are side elevational views of electrodes heating tissue.

FIG. 64 is a side elevational view of an electrode assembly with ringelectrodes.

FIG. 65 is a side elevational view of a shielded electrode heatingtissue.

FIG. 66 is a side elevational view of an arcuate shielded electrodeheating tissue.

FIGS. 67A-71B show isotherms and corresponding lesions.

FIG. 72 is an isometric view of a delivery device with a distallydistensible, expandable element in a delivery configuration.

FIG. 73 is a cross-sectional view of an ablation assembly taken along aline 73-73.

FIG. 74 an isometric view of a delivery device with the distallydistensible, expandable element in a deployed configuration.

FIG. 75 is a cross-sectional view of an ablation assembly taken along aline 75-75.

FIG. 76 is a cross-sectional view of an elongate body taken along a line76-76 of FIG. 75.

FIG. 77 is an isometric view of a delivery device with a distallydistensible, expandable element carrying an electrode.

FIG. 78 is an isometric view of the expandable element in an inflatedstate.

FIG. 79 is a cross-sectional view of the ablation assembly taken along aline 79-79 of FIG. 77.

FIG. 80 is a cross-sectional view of the delivery device taken along aline 80-80 of FIG. 78.

FIG. 81 is a cross-sectional view of an elongate body taken along a line81-81 of FIG. 80.

FIG. 82 is an isometric view of a delivery device with an independentlycooled distally distensible, expandable element and electrode.

FIG. 83 is an isometric view of the distally distensible, expandableelement in a delivery configuration.

FIG. 84 is a cross-sectional view of the delivery device taken along aline 84-84 of FIG. 82.

FIG. 85 is a cross-sectional view of an elongate body of FIG. 86 takenalong a line 85-85.

FIG. 86 is a cross-sectional view of the delivery device taken along aline 86-86 of FIG. 82.

FIGS. 87A-89B show isotherms and corresponding lesions.

FIG. 90 is an isometric view of a delivery device with discharge ports.

FIG. 91 is a cross-sectional view of the delivery device taken along aline 91-91 of FIG. 90.

FIG. 92 is a longitudinal cross-sectional view of a delivery device withlongitudinally spaced apart discharge ports.

FIG. 93 is an isometric view of a delivery device that performs athrottling process.

FIG. 94 is a cross-sectional view of the delivery device taken along aline 94-94 of FIG. 93.

FIG. 95 is an isometric view of a delivery device in a deliveryconfiguration.

FIG. 96 is an isometric view of the delivery device in a deployedconfiguration.

FIG. 97 is a detailed cross-sectional view of a distal section of thedelivery device.

FIG. 98 is an isometric view of a delivery device with positioningfeatures.

FIG. 99 is a top plan view of the delivery device of FIG. 98.

FIG. 100 is a cross-sectional view of the delivery device taken along aline 100-100.

FIG. 101 is a longitudinal cross-sectional view of a delivery apparatusand a delivery device.

FIG. 102 is an isometric, cutaway view of a delivery apparatus holding adelivery device.

FIG. 103 is an isometric view of the delivery device ready to bedeployed.

FIG. 104 is an isometric view of the delivery device of FIG. 103 in adeployed configuration.

FIG. 105 is a side elevational view of an ablation assembly in adeployed configuration.

FIG. 105A is a cross-sectional view of an electrode taken along a line105A-105A of FIG. 105.

FIG. 106 is a side elevational view of an ablation assembly with anexpandable element in a partially inflated state and an inflated energyemitter assembly.

FIG. 107 is a side elevational view of the ablation assembly with adeflated energy emitter assembly.

FIG. 108 is a side elevational view of the ablation assembly with thedeflated energy emitter assembly in a collapsed configuration.

FIG. 109 is an isometric view of a delivery device with an independentlydeployable electrode assembly and expandable element.

FIG. 110 is an isometric view of the delivery device with the expandableelement in a deployed state.

FIG. 111 is an isometric view of the electrode assembly and theexpandable element in delivery states.

FIG. 112 is a cross-sectional view of the delivery device taken along aline 112-112 of FIG. 111.

FIG. 113 is a cross-sectional view of the delivery device taken along aline 113-113 of FIG. 111.

FIG. 114 is an isometric view of a delivery device with acircumferentially expandable electrode.

FIG. 115 is an isometric view of the electrode of FIG. 114 in anexpanded state.

FIG. 116 is an isometric view of an expanded element holding theelectrode in the expanded state.

FIG. 117 is an isometric view of a delivery device in accordance withanother embodiment.

FIG. 118 is an isometric view of the delivery device in an expandedstate.

FIG. 119 is an isometric view of the delivery device in an expandedstate.

DETAILED DESCRIPTION

FIG. 1 illustrates human lungs 10 having a left lung 11 and a right lung12. A trachea 20 extends downwardly from the nose and mouth and dividesinto a left main bronchus 21 and a right main bronchus 22. The left mainbronchus 21 and right main bronchus 22 each branch to form lobar,segmental bronchi, and sub-segmental bronchi, which have successivelysmaller diameters and shorter lengths in the outward direction (i.e.,the distal direction). A main pulmonary artery 30 originates at a rightventricle of the heart and passes in front of a lung root 24. At thelung root 24, the artery 30 branches into a left and right pulmonaryartery, which in turn branch to form a network of branching bloodvessels. These blood vessels can extend alongside airways of a bronchialtree 27.

The bronchial tree 27 includes the left main bronchus 21, the right mainbronchus 22, bronchioles, and alveoli. Vagus nerves 41, 42 extendalongside the trachea 20 and branch to form nerve trunks 45.

The left and right vagus nerves 41, 42 originate in the brainstem, passthrough the neck, and descend through the chest on either side of thetrachea 20. The vagus nerves 41, 42 spread out into nerve trunks 45 thatinclude the anterior and posterior pulmonary plexuses that wrap aroundthe trachea 20, the left main bronchus 21, and the right main bronchus22. The nerve trunks 45 also extend along and outside of the branchingairways of the bronchial tree 27. Nerve trunks 45 are the main stem of anerve, comprising a bundle of nerve fibers bound together by a toughsheath of connective tissue.

The primary function of the lungs 10 is to exchange oxygen from air intothe blood and to exchange carbon dioxide from the blood to the air. Theprocess of gas exchange begins when oxygen rich air is pulled into thelungs 10. Contraction of the diaphragm and intercostal chest wallmuscles cooperate to decrease the pressure within the chest to cause theoxygen rich air to flow through the airways of the lungs 10. Forexample, air passes through the mouth and nose, the trachea 20, thenthrough the bronchial tree 27. The air is ultimately delivered to thealveolar air sacs for the gas exchange process.

Oxygen poor blood is pumped from the right side of the heart through thepulmonary artery 30 and is ultimately delivered to alveolar capillaries.This oxygen poor blood is rich in carbon dioxide waste. Thinsemi-permeable membranes separate the oxygen poor blood in capillariesfrom the oxygen rich air in the alveoli. These capillaries wrap aroundand extend between the alveoli. Oxygen from the air diffuses through themembranes into the blood, and carbon dioxide from the blood diffusesthrough the membranes to the air in the alveoli. The newly oxygenenriched blood then flows from the alveolar capillaries through thebranching blood vessels of the pulmonary venous system to the heart. Theheart pumps the oxygen rich blood throughout the body. The oxygen spentair in the lung is exhaled when the diaphragm and intercostal musclesrelax and the lungs and chest wall elastically return to the normalrelaxed states. In this manner, air can flow through the branchingbronchioles, the bronchi 21, 22, and the trachea 20 and is ultimatelyexpelled through the mouth and nose.

FIG. 2 shows a treatment system 200 capable of performing treatments toadjust air flow during expiration or inhalation, or both. To decreaseair flow resistance to increase gas exchange, the treatment system 200can be used to enlarge (e.g., dilate) airways. In some procedures, nervetissue, such as nerve tissue of a nerve trunk inside or outside of thelungs, can be affected to dilate airways. The nervous system providescommunication between the brain and the lungs 10 using electrical andchemical signals. A network of nerve tissue of the autonomic nervoussystem senses and regulates activity of the respiratory system and thevasculature system. Nerve tissue includes fibers that use chemical andelectrical signals to transmit sensory and motor information from onebody part to another. For example, the nerve tissue can transmit motorinformation in the form of nervous system input, such as a signal thatcauses contraction of muscles or other responses. The fibers can be madeup of neurons. The nerve tissue can be surrounded by connective tissue,i.e., epineurium. The autonomic nervous system includes a sympatheticsystem and a parasympathetic system. The sympathetic nervous system islargely involved in “excitatory” functions during periods of stress. Theparasympathetic nervous system is largely involved in “vegetative”functions during periods of energy conservation. The sympathetic andparasympathetic nervous systems are simultaneously active and generallyhave reciprocal effects on organ systems. While innervation of the bloodvessels originates from both systems, innervation of the airways arelargely parasympathetic in nature and travel between the lung and thebrain in the right vagus nerve 42 and the left vagus nerve 41.

Any number of procedures can be performed on one or more of these nervetrunks 45 to affect the portion of the lung associated with those nervetrunks. Because some of the nerve tissue in the network of nerve trunks45 coalesce into other nerves (e.g., nerves connected to the esophagus,nerves though the chest and into the abdomen, and the like), thetreatment system 200 can treat specific sites to minimize, limit, orsubstantially eliminate unwanted damage of those other nerves. Somefibers of anterior and posterior pulmonary plexuses coalesce into smallnerve trunks which extend along the outer surfaces of the trachea 20 andthe branching bronchi and bronchioles as they travel outward into thelungs 10. Along the branching bronchi, these small nerve trunkscontinually ramify with each other and send fibers into the walls of theairways, as discussed in connection with FIGS. 4 and 5. Variousprocedures that may be performed with at least some of the devices andmethods of the present invention are described in copending applicationSer. No. 12/463,304 filed on May 8, 2009, which is incorporated hereinby reference in its entirety.

The treatment system 200 can affect specific nerve tissue, such as vagusnerve tissue, associated with particular sites of interest. Vagus nervetissue includes efferent fibers and afferent fibers oriented parallel toone another within a nerve branch. The efferent nerve tissue transmitssignals from the brain to airway effector cells, mostly airway smoothmuscle cells and mucus producing cells. The afferent nerve tissuetransmits signals from airway sensory receptors, which respond toirritants, and stretch to the brain.

While efferent nerve tissue innervates smooth muscle cells all the wayfrom the trachea 20 to the terminal bronchioles, the afferent fiberinnervation is largely limited to the trachea 20 and larger bronchi.There is a constant, baseline tonic activity of the efferent vagus nervetissues to the airways which causes a baseline level of smooth musclecontraction and mucous secretion. The treatment system 200 can affectthe efferent and/or the afferent tissues to control airway smooth muscle(e.g., innervate smooth muscle), mucous secretion, nervous mediatedinflammation, and tissue fluid content (e.g., edema). The contraction ofairway smooth muscle, excess mucous secretion, inflammation, and airwaywall edema associated with pulmonary diseases often results inrelatively high air flow resistance causing reduced gas exchange anddecreased lung performance.

In certain procedures, the treatment system 200 can be used to attenuatethe transmission of signals traveling along the vagus nerves 41, 42 thatcause or mediate muscle contractions, mucus production, inflammation,edema, and the like. Attenuation can include, without limitation,hindering, limiting, blocking, and/or interrupting the transmission ofsignals. For example, the attenuation can include decreasing signalamplitude of nerve signals or weakening the transmission of nervesignals. Decreasing or stopping nervous system input to distal airwayscan alter airway smooth muscle tone, airway mucus production, airwayinflammation, and the like, thereby controlling airflow into and out ofthe lungs 10. Decreasing or stopping sensory input from the airways andlungs to local effector cells or to the central nervous system can alsodecrease reflex bronchoconstriction, reflex mucous production, releaseof inflammatory mediators, and nervous system input to other cells inthe lungs or organs in the body that may cause airway wall edema. Insome embodiments, the nervous system input can be decreased tocorrespondingly decrease airway smooth muscle tone. In some embodiments,the airway mucus production can be decreased a sufficient amount tocause a substantial decrease in coughing and/or in airflow resistance.In some embodiments, the airway inflammation can be decreased asufficient amount to cause a substantial decrease in airflow resistanceand ongoing inflammatory injury to the airway wall. Signal attenuationmay allow the smooth muscles to relax, prevent, limit, or substantiallyeliminate mucus production by mucous producing cells, and decreaseinflammation. In this manner, healthy and/or diseased airways can bealtered to adjust lung function. After treatment, various types ofquestionnaires or tests can be used to assess the subject's response tothe treatment. If needed or desired, additional procedures can beperformed to reduce the frequency of coughing, decrease breathlessness,decrease wheezing, and the like.

Main bronchi 21, 22 (i.e., airway generation 1) of FIGS. 1 and 2 can betreated to affect distal portions of the bronchial tree 27. In someembodiments, the left and right main bronchi 21, 22 are treated atlocations along the left and right lung roots 24 and outside of the leftand right lungs 11, 12. Treatment sites can be distal to where vagusnerve branches connect to the trachea and the main bronchi 21, 22 andproximal to the lungs 11, 12. A single treatment session involving twotherapy applications can be used to treat most of or the entirebronchial tree 27. Substantially all of the bronchial branches extendinginto the lungs 11, 12 may be affected to provide a high level oftherapeutic effectiveness. Because the bronchial arteries in the mainbronchi 21, 22 have relatively large diameters and high heat sinkingcapacities, the bronchial arteries may be protected from unintendeddamage due to the treatment.

FIG. 3 shows a delivery device in the form of a catheter system 204extending through a delivery apparatus 206. The catheter system 204 cantreat airways of the main bronchi 21, 22, as well as airways that aredistal to the main bronchi 21, 22. An ablation assembly 208 can bepositioned outside the lung which is within the right or left mainbronchi, the lobar bronchii, and bronchus intermedius. The intermediatebronchus is the portion of the right main bronchus and the origin of themiddle and lower lobar bronchii. The ablation assembly 208 can bepositioned in higher generation airways (e.g., airway generations >2) toaffect remote distal portions of the bronchial tree 27. The cathetersystem 204 can be navigated through tortuous airways to perform a widerange of different procedures, such as, for example, denervation of aportion of a lobe, an entire lobe, multiple lobes, or one lung or bothlungs. In some embodiments, the lobar bronchi are treated to denervatelung lobes. For example, one or more treatment sites along a lobarbronchus may be targeted to denervate an entire lobe connected to thatlobar bronchus. Left lobar bronchi can be treated to affect the leftsuperior lobe and/or the left inferior lobe. Right lobar bronchi can betreated to affect the right superior lobe, the right middle lobe, and/orthe right inferior lobe. Lobes can be treated concurrently orsequentially. In some embodiments, a physician can treat one lobe. Basedon the effectiveness of the treatment, the physician can concurrently orsequentially treat additional lobe(s). In this manner, differentisolated regions of the bronchial tree can be treated.

Each segmental bronchus may be treated by delivering energy to a singletreatment site along each segmental bronchus. For example, the cathetersystem 204 can deliver energy to each segmental bronchus of the rightlung. In some procedures, ten applications of energy can treat most ofor substantially all of the right lung. In some procedures, most orsubstantially all of both lungs are treated using less than thirty-sixdifferent applications of energy. Depending on the anatomical structureof the bronchial tree, segmental bronchi can often be denervated usingone or two applications of energy.

Function of other tissue or anatomical features, such as the mucousglands, cilia, smooth muscle, body vessels (e.g., blood vessels), andthe like can be maintained when nerve tissue is ablated. Nerve tissueincludes nerve cells, nerve fibers, dendrites, and supporting tissue,such as neuroglia. Nerve cells transmit electrical impulses, and nervefibers are prolonged axons that conduct the impulses. The electricalimpulses are converted to chemical signals to communicate with effectorcells or other nerve cells. By way of example, a portion of an airway ofthe bronchial tree 27 can be denervated to attenuate one or more nervoussystem signals transmitted by nerve tissue. Denervating can includedamaging all of the nerve tissue of a section of a nerve trunk along anairway to stop substantially all the signals from traveling through thedamaged section of the nerve trunk to more distal locations along thebronchial tree or from the bronchial tree more proximally to the centralnervous system. Additionally, signals that travel along nerve fibersthat go directly from sensory receptors (e.g., cough and irritantreceptors) in the airway to nearby effector cells (e.g., postganglionicnerve cells, smooth muscle cells, mucous cells, inflammatory cells, andvascular cells) will also be stopped. If a plurality of nerve trunksextends along the airway, each nerve trunk can be damaged. As such, thenerve supply along a section of the bronchial tree can be cut off. Whenthe signals are cut off, the distal airway smooth muscle can relaxleading to airway dilation, mucous cells decrease mucous production, orinflammatory cells stop producing airway wall swelling and edema. Thesechanges reduce airflow resistance so as to increase gas exchange in thelungs 10, thereby reducing, limiting, or substantially eliminating oneor more symptoms, such as breathlessness, wheezing, chest tightness, andthe like. Tissue surrounding or adjacent to the targeted nerve tissuemay be affected but not permanently damaged. In some embodiments, forexample, the bronchial blood vessels along the treated airway candeliver a similar amount of blood to bronchial wall tissues and thepulmonary blood vessels along the treated airway can deliver a similaramount of blood to the alveolar sacs at the distal regions of thebronchial tree 27 before and after treatment. These blood vessels cancontinue to transport blood to maintain sufficient gas exchange. In someembodiments, airway smooth muscle is not damaged to a significantextent. For example, a relatively small section of smooth muscle in anairway wall which does not appreciably impact respiratory function maybe reversibly altered. If energy is used to destroy the nerve tissueoutside of the airways, a therapeutically effective amount of energydoes not reach a significant portion of the non-targeted smooth muscletissue.

In some embodiments, one of the left and right main bronchi 21, 22 istreated to treat one side of the bronchial tree 27. The other mainbronchus 21, 22 can be treated based on the effectiveness of the firsttreatment. For example, the left main bronchus 21 can be treated totreat the left lung 11. The right main bronchus 22 can be treated totreat the right lung 12. In some embodiments, a single treatment systemcan damage the nerve tissue of one of the bronchi 21, 22 and can damagethe nerve tissue of the other main bronchus 21, 22 without removing thetreatment system from the trachea 20. Nerve tissue positioned along themain bronchi 21, 22 can thus be damaged without removing the treatmentsystem from the trachea 20. In some embodiments, a single procedure canbe performed to conveniently treat substantially all, or at least asignificant portion (e.g., at least 50%, 70%, 80%, 90% of the bronchialairways), of the patient's bronchial tree. In other procedures, thetreatment system can be removed from the patient after treating one ofthe lungs 11, 12. If needed, the other lung 11, 12 can be treated in asubsequent procedure.

FIG. 4 is a transverse cross-sectional view of a healthy airway 100,illustrated as a bronchial tube. The ablation assembly 208 is in apartially expanded state and positioned along the lumen 101 defined byan inner surface 102 of the airway 100. The illustrated inner surface102 is defined by a folded layer of epithelium 110 surrounded by stroma112 a. A layer of smooth muscle tissue 114 surrounds the stroma 112 a. Alayer of stroma 112 b is between the muscle tissue 114 and connectivetissue 124. Mucous glands 116, cartilage plates 118, blood vessels 120,and nerve fibers 122 are within the stroma layer 112 b. Bronchial arterybranches 130 and nerve trunks 45 are exterior to a wall 103 of theairway 100. The illustrated arteries 130 and nerve trunks 45 are withinthe connective tissue 124 surrounding the airway wall 103 and can beoriented generally parallel to the airway 100. In FIG. 1, for example,the nerve trunks 45 originate from the vagus nerves 41, 42 and extendalong the airway 100 towards the air sacs. The nerve fibers 122 are inthe airway wall 103 and extend from the nerve trunks 45 to the muscletissue 114. Nervous system signals are transmitted from the nerve trunks45 to the muscle 114 and mucous glands 116 via the nerve fibers 122.Additionally, signals are transmitted from sensory receptors (e.g.,cough, irritant, and stretch) through the nerve trunks 45 to the centralnervous system.

Cilia can be damaged, excited, or otherwise altered to elicit a desiredresponse along the epithelium 110 in order to control (e.g., increase ordecrease) mucociliary transport. Many particles are inhaled as a personbreathes, and the airways function as a filter to remove the particlesfrom the air. The mucociliary transport system functions as aself-cleaning mechanism for all the airways throughout the lungs 10. Themucociliary transport is a primary method for mucus clearance fromdistal portions of the lungs 10, thereby serving as a primary immunebarrier for the lungs 10. For example, the inner surface 102 of FIG. 4can be covered with cilia and coated with mucus. As part of themucociliary transport system, the mucus entraps many inhaled particles(e.g., unwanted contaminates such as tobacco smoke) and moves theseparticles towards the larynx. The ciliary beat of cilia moves acontinuous carpet of mucus and entrapped particles from the distalportions of the lungs 10 past the larynx and to the pharynx forexpulsion from the respiratory system. The ablation assembly 208 candamage the cilia to decrease mucociliary transport or excite the ciliato increase mucociliary transport.

The ablation assembly 208 can selectively treat target regions inside ofthe airway wall 103 (e.g., anatomical features in the stromas 112 a, 112b). For example, the mucous glands 116 can be damaged to reduce mucusproduction a sufficient amount to prevent the accumulation of mucus thatcauses increased air flow resistance while preserving enough mucusproduction to maintain effective mucociliary transport, if needed ordesired. Nerve branches/fibers passing through the airway wall 103 orother anatomical features in the airway wall 103 can also be destroyed.

If an ablation element is an RF electrode 214, the electrode 214 can bebrought into contact with or proximate to the inner surface 102. The RFelectrode 214 can output RF energy which travels through the tissue andis converted into heat. The heat causes formation of a lesion. The RFenergy can be directed radially outward towards the nerve truck 45 andbetween the cartilage plates 118. The nerve trunk 45 can be damagedwithout causing appreciable damage to the adjacent cartilage plates 118.Damage to other non-targeted regions (e.g., the epithelium) can also bekept at or below an acceptable level.

Natural body functions can help prevent, reduce, or limit damage totissue. Blood within the blood vessels 130 can absorb thermal energy andcan then carry the thermal energy away from the heated section of thebranches 130. In this manner, blood can mitigate or avoid damage to theblood vessels 130. After the treatment is performed, the bronchialartery branches 130 can continue to maintain the health of lung tissue.In some embodiments, a sufficient amount of RF energy is delivered tothe nerve trunk 45 to destroy an entire longitudinal section of thenerve trunk 45 while keeping the amount of energy that reaches the bloodvessels 130 below an amount that causes tissue destruction of the vessel130. Thus, therapies can be performed without damaging to anysignificant extent other regions of the airway 100, even regions thatare adjacent to the treatment site.

Treatment efficacy can be evaluated based at least in part on one ormore airway attributes, pulmonary function tests, exercise capacitytests, and/or questionnaires. Patients can be evaluated to track andmonitor their progress. If needed or desired, additional procedures canbe performed until desired responses are achieved. Different types ofinstruments for evaluating airway attributes may be used. Duringablation, feedback from an instrument can indicate whether the targetedtissue has been ablated. Once targeted tissue is ablated, therapy can bediscontinued to minimize or limit collateral damage, if any, to healthyuntargeted tissue.

Different attributes of airways can be evaluated to determine proceduresto be performed. Such airway attributes include, without limitation,physical properties of airways (e.g., airway compliance, contractileproperties, etc.), airway resistance, dimensions of airway lumens (e.g.,shapes of airways, diameters of airways, etc.), responsiveness ofairways (e.g., responsiveness to stimulation), muscle characteristics(e.g., muscle tone, muscle tension, etc.), inflammatory cells,inflammatory cytokines, or the like. In some embodiments, changes ofairway muscle characteristics can be monitored by measuring pressurechanges in the ablation assembly 208, which is inflated to a knownpressure. Based on pressure changes, a physician determines the effects,if any, of the treatment, including, without limitation, whethertargeted tissue has been stimulated, ablated, or the like.

FIG. 5 is a transverse cross-sectional view of a portion of the airway100 that has smooth muscle tissue 114 in a contracted state, mucus 150from hypertrophied mucous glands 116, and inflammatory swelling andedema fluid thickening the airway wall 103. The contracted muscle tissue114, the mucus 150, and thickened airway wall 103 cooperate to partiallyobstruct the lumen 101 resulting in a relatively high air flowresistance. The nerve tissue 45 is damaged to relax the muscle tissue114 to dilate the airway 100 to reduce air flow resistance, therebyallowing more air to reach the alveolar sacs for the gas exchangeprocess. Decreases in airway resistance may indicate that passageways ofairways are opening, for example in response to attenuation of nervoussystem input to those airways. The decrease of airway resistanceassociated with treating low generation airways (e.g., main bronchi,lobar bronchi, segmental bronchi) may be greater than the amount ofdecrease of airway resistance associated with treating high generationairways (e.g., subsegmental bronchioles). A physician can selectappropriate airways for treatment to achieve a desired decrease inairway resistance and can be measured at a patient's mouth, a bronchialbranch that is proximate to the treatment site, a trachea, or any othersuitable location. The airway resistance can be measured beforeperforming the therapy, during the therapy, and/or after the therapy. Insome embodiments, airway resistance is measured at a location within thebronchial tree by, for example, using a vented treatment system thatallows for respiration from areas that are more distal to the treatmentsite.

Energy can be used to damage target regions. As used herein, the term“energy” is broadly construed to include, without limitation, thermalenergy, cryogenic energy (e.g., cooling energy), electrical energy,acoustic energy (e.g., ultrasonic energy), radio frequency energy,pulsed high voltage energy, mechanical energy, ionizing radiation,optical energy (e.g., light energy), and combinations thereof, as wellas other types of energy suitable for treating tissue. In someembodiments, the catheter system 204 delivers energy and one or moresubstances (e.g., radioactive seeds, radioactive materials, etc.),treatment agents, and the like. Exemplary non-limiting treatment agentsinclude, without limitation, one or more antibiotics, anti-inflammatoryagents, pharmaceutically active substances, bronchoconstrictors,bronchodilators (e.g., beta-adrenergic agonists, anticholinergics,etc.), nerve blocking drugs, photoreactive agents, or combinationsthereof. For example, long acting or short acting nerve blocking drugs(e.g., anticholinergics) can be delivered to the nerve tissue totemporarily or permanently attenuate signal transmission. Substances canalso be delivered directly to the nerves 122 or the nerve trunks 45, orboth, to chemically damage the nerve tissue.

FIGS. 6 and 7 show the effect produced by superficial and deep heatingby RF energy and superficial cooling by circulating coolant in theablation assembly 208. A cooling section 209 of the ablation assembly208 contains coolant to cool tissue adjacent to a tissue-contactingportion 215 of the energy emitter assembly 220 when energy is outputted.The cooling section 209 can absorb a sufficient amount of thermal energyfrom the airway wall 100 to limit or prevent damage to the tissuebetween the energy emitter assembly 220 and the nerve tissue or othertargeted tissue.

FIG. 7 shows a cross-sectional temperature profile in a section of theairway wall through which the RF energy is delivered to ablate tissue.The terms “ablate” or “ablation,” including derivatives thereof,include, without limitation, substantial altering of electricalproperties, mechanical properties, chemical properties, or otherproperties of tissue. As used herein, the term “ablate,” includingvariations thereof, refers, without limitation, to destroying or topermanently damaging, injuring, or traumatizing tissue. For example,ablation may include localized tissue destruction, cell lysis, cell sizereduction, necrosis, or combinations thereof. In the context ofpulmonary ablation applications, the term “ablation” includessufficiently altering nerve tissue properties to substantially blocktransmission of electrical signals through the ablated nerve tissue.

FIG. 6 is a graph with a horizontal axis corresponding to the depth intothe tissue of the airway wall from the point of contact with orproximate to the electrode 214 in millimeters with a vertical axiscorresponding to the temperature of the tissue in degrees Centigrade.Temperatures in the figures are in degrees Centigrade, unless indicatedotherwise. The point “0” on the graph corresponds to the point or areaof contact between the electrode 214 and the tissue of the airway wall.Three curves A, B, and C are shown in the graph and correspond to threedifferent power levels of radio frequency energy being delivered intothe tissue. The temperature on the graph is up to about 100° C. Thetemperature of about 100° C., or slightly less, has been shown becauseit is considered to be an upper limit for tissue temperature during RFablation. At approximately 90° C., tissue fluids begin to boil andtissue coagulates and chars, thereby greatly increasing its impedanceand compromising its ability to transfer RF energy into the tissue ofthe airway wall. Thus, it may be desirable to have tissue temperaturesremain below about 90° C. At about 50° C., a line 216 represents thetemperature above which tissue cell death occurs and below which tissuessuffer no substantial long term effects (or any long term effects).

Curve A shown in FIG. 6 represents what occurs with and without coolingof the electrode 214 at a relatively low power level, for example, about10 watts of RF energy. Curve A is divided into three segments A1, A2,and A3. The broken line segment A2 represents a continuation of theexponential curve A3 when no cooling applied. As can be seen by curve A,the temperature of the electrode-tissue interface without coolingreaches 80° C. and decreases exponentially as the distance into thetissue of the airway 100 increases. As shown, the curve A3 crosses the50° C. tissue cell death boundary represented by the line 216 at a depthof about 5 millimeters. Thus, without electrode cooling, the depth ofcell death that would occur would be approximately 5 millimeters asrepresented by the distance d1. Further cell death would stop at thispower level.

If active cooling is employed, the temperature drops to a much lowerlevel, for example, about 35° C. as represented by the curve A1 at theelectrode-tissue interface at 0 millimeters in distance. Since thistemperature is below 50° C., cell death will not begin to occur until adistance of d2 at the point where the curve A2 crosses the cell deathline at 50° C., for example, a depth of 3 millimeters from the surface.Cell death will occur at depths from 3 millimeters to 5 millimeters asrepresented by the distance d3. Such a cooled ablation procedure isadvantageous because it permits cell death and tissue destruction tooccur at a distance (or a range of distances) from the electrode-tissueinterface without destroying the epithelium and the tissue immediatelyunderlying the same. In some embodiments, the nerve tissues runningalong the outside of the airway can be ablated without damaging theepithelium or underlying structures, such as the stroma and smoothmuscle cells.

The curve B represents what occurs with and without cooling of theelectrode at a higher power level, for example, 20 watts of RF energy.Segment B2 of curve B represents a continuation of the exponential curveof the segment B3 without cooling. As can be seen, the temperature atthe electrode-tissue interface approaches 100° C. which may beundesirable because that is a temperature at which boiling of tissuefluid and coagulation and charring of tissue at the tissue-electrodeinterface will occur, thus making significantly increasing the tissueimpedance and compromising the ability to deliver additional RF energyinto the airway wall. By providing active cooling, the curve B1 showsthat the temperature at the electrode-tissue interface drops toapproximately 40° C. and that cell death occurs at depths of twomillimeters as represented by d4 to a depth of approximately 8millimeters where the curve B3 crosses the 50° C. tissue cell deathboundary. Thus, it can be seen that it is possible to provide a muchdeeper and larger region of cell death using the higher power levelwithout reaching an undesirable high temperature (e.g., a temperaturethat would result in coagulation and charring of tissue at theelectrode-tissue interface). The systems can be used to achieve celldeath below the epithelial surface of the airway so that the surfaceneed not be destroyed, thus facilitating early recovery by the patientfrom a treatment.

The curve C represents a still higher power level, for example, 40 wattsof RF energy. The curve C includes segments C1, C2, and C3. The brokenline segment C2 is a continuation of the exponential curve C3. SegmentC2 shows that the temperature at the electrode-tissue interface farexceeds 100° C. and would be unsuitable without active cooling. Withactive cooling, the temperature at the electrode-tissue interfaceapproaches 80° C. and gradually increases and approaches 95° C. and thendrops off exponentially to cross the 50° C. cell death line 216 at adistance of about 15 millimeters from the electrode-tissue interface atthe epithelial surface of the airway represented by the distance d6.Because the starting temperature is above the 50° C. cell death line216, tissue cell death will occur from the epithelial surface to a depthof about 15 millimeters to provide large and deep regions of tissuedestruction.

In FIG. 7, arrows 218 represent movement of the coolant through theenergy emitter assembly 220. Arrows 222 represent movement of thecoolant through a deployable element, illustrated as a distensible andthermally conductive balloon 212. Isothermal curves show thetemperatures that are reached at the electrode 214 and at differentdepths into the airway wall 100 from the electrode-tissue interface whenpower is applied to the electrode 214 and coolant (e.g., a roomtemperature saline solution or iced saline) is delivered to the balloon212. The term “element” in the context of “expandable element” includesa discrete element or a plurality of discrete elements. By way ofexample, an expandable element can be a single balloon or a plurality ofballoons in fluid communication with one another.

By adjusting the rate of power delivery to the electrode 214, the rateat which coolant (e.g., saline solution) is passed into the balloon 212,the temperature of the saline solution, and the size of the balloon 212,and the exact contour and temperature of the individual isotherms can bemodified. For example, by selecting the proper temperature and flow rateof saline and the rate of power delivery to the electrode, it ispossible to achieve temperatures in which isotherm A=60° C., B=55° C.,C=50° C., D=45° C., E=40° C., and F=37° C. Further adjustments make itpossible to achieve temperatures where isotherm A=50° C., B=47.5° C.,C=45° C., D=42.5° C., E=40° C., and F=37° C. Only those areas containedwithin the 50° C. isotherm will be heated enough to induce cell death.In some procedures, tissue at a depth of about 2 mm to about 8 mm in theairway wall can be ablated while other non-targeted tissues at a depthless than 2 mm in the airway wall are kept at a temperature below attemperature that would cause cell death. The coolant 218 can absorbenergy to cool the tissue-contacting portion 215 of the energy emitterassembly 220 while the balloon 212 holds the energy emitter assembly 220against the airway 100.

Referring to FIG. 8, the catheter system 204 includes a control module210 coupled to a catheter 207 having an elongate body in the form of ashaft 230 and the ablation assembly 208 coupled to the distal end of theshaft 230. Ablation assembly 208 comprises an energy emitter assembly220 extending from the elongate shaft 230 and wrapping around theballoon 212. The balloon 212 can be inflated from a collapsed state tothe illustrated expanded state. As the balloon 212 inflates, theelectrode 214 can be moved towards the airway wall. The inflated balloon212 can help hold the electrode 214 near (e.g., proximate or in contactwith) tissue through which energy is delivered. The coolant can absorbthermal energy to cool the balloon 212 or the energy emitter assembly220, or both. This in turn cools the outer surface of the airway wall.

The control module 210 generally includes a controller 244 and a fluiddelivery system 246. The controller 244 includes, without limitation,one or more processors, microprocessors, digital signal processors(DSPs), field programmable gate arrays (FPGA), and/orapplication-specific integrated circuits (ASICs), memory devices, buses,power sources, and the like. For example, the controller 244 can includea processor in communication with one or more memory devices. Buses canlink an internal or external power supply to the processor. The memoriesmay take a variety of forms, including, for example, one or morebuffers, registers, random access memories (RAMs), and/or read onlymemories (ROMs). The controller 244 may also include a display 245, suchas a screen, and an input device 250. The input device 250 can include akeyboard, touchpad, or the like and can be operated by a user to controlthe catheter 207.

The controller 244 can store different programs. A user can select aprogram that accounts for the characteristics of the tissue and desiredtarget region. For example, an air-filled lung can have relatively highimpedance, lymph nodes have medium impedance, and blood vessels haverelatively low impedance. The controller 244 can determine anappropriate program based on the impedance. A differential coolingprogram can be executed to deliver different temperature coolantsthrough the balloon 212 and the energy emitter assembly 220. Thetemperature difference can be at least 10° C. Performance can beoptimized based on feedback from sensors that detect temperatures,tissue impedance, or the like. For example, the controller 244 cancontrol operation of the ablation assembly 208 based on a surfacetemperature of the tissue to which energy is delivered. If the surfacetemperature becomes excessively hot, cooling can be increased and/orelectrode power decreased in order to produce deep lesions whileprotecting surface tissues.

An internal power supply 248 (illustrated in dashed line in FIG. 8) cansupply energy to the electrode 214 and can be an energy generator, suchas a radiofrequency (RF) electrical generator. RF energy can beoutputted at a desired frequency. Example frequencies include, withoutlimitation, frequencies in a range of about 50 KHZ to about 1,000 MHZ.When the RF energy is directed into tissue, the energy is convertedwithin the tissue into heat causing the temperature of the tissue to bein the range of about 40° C. to about 99° C. The RF energy can beapplied for about 1 second to about 120 seconds. In some embodiments,the RF generator 248 has a single channel and delivers approximately 1to 25 watts of RF energy and possesses continuous flow capability. Otherranges of frequencies, time intervals, and power outputs can also beused. Alternatively, the internal power supply 248 can be an energystorage device, such as one or more batteries. Electrical energy can bedelivered to the energy emitter assembly 220, which converts theelectrical energy to RF energy or another suitable form of energy. Otherforms of energy that may be delivered include microwave, ultrasound,direct current, or laser energy. Alternatively, cryogenic ablation maybe utilized wherein a fluid at cryogenic temperatures is deliveredthrough the shaft 230 to cool a cryogenic heat exchanger on the ablationassembly 208.

The fluid delivery system 246 includes a fluid source 260 coupled to asupply line 268 and a fluid receptacle 262 coupled to a return line 272.The fluid source 260 can include a container (e.g., a bottle, acanister, a tank, or other type of vessel for holding fluid) held in ahousing unit 264. In pressurizable embodiments, the fluid source 260includes one or more pressurization devices (e.g., one or more pumps,compressors, or the like) that pressurize coolant. Temperature controldevices (e.g., Peltier devices, heat exchangers, or the like) can coolor recondition the fluid. The fluid can be a coolant comprising saline,de-ionized water, refrigerant, cryogenic fluid, gas, or the like. Inother embodiments, the fluid source 260 can be an insulated containerthat holds and delivers a chilled coolant to the supply line 268. Thecoolant flows distally through the elongate shaft 230 into the ablationassembly 208. Coolant in the ablation assembly 208 flows proximallythrough the elongate shaft 230 to the return line 272. The coolantproceeds along the return line 272 and ultimately flows into the fluidreceptacle 262.

The balloon 212 optionally has a sensor 247 (illustrated in dashed line)that is communicatively coupled to the controller 244. The controller244 can command the catheter 207 based on signals from the sensor 247(e.g., a pressure sensor, a temperature sensor, a thermocouple, apressure sensor, a contact sensor, or the like). Sensors can also bepositioned on energy emitter assembly 220, along the elongate shaft 230or at any other location. The controller 244 can be a closed loop systemor an open loop system. For example, in a closed loop system, theelectrical energy is delivered to the electrode 214 based upon feedbacksignals from one or more sensors configured to transmit (or send) one ormore signals indicative of one or more tissue characteristics, energydistribution, tissue temperatures, or any other measurable parameters ofinterest. Based on those readings, the controller 244 adjusts operationof the electrode 214. Alternatively, in an open loop system, theoperation of the electrode 214 is set by user input. For example, theuser can observe tissue temperature or impedance readings and manuallyadjust the power level delivered to the electrode 214. Alternatively,the power can be set to a fixed power mode. In yet other embodiments, auser can repeatedly switch between a closed loop system and an open loopsystem.

To effectively cool the electrode 214, a conduit 234 coupled to theelectrode 214 is fluidly coupled to a coolant delivery lumen within theshaft 230 to receive coolant therefrom. Alternatively, flow diverterswithin the balloon 212 can direct some or all of the coolant in theballoon 212 towards the electrode 214 or a balloon sidewall and mayprovide a separate cooling channel for the electrode 214. In someembodiments, one or more cooling channels extend through the electrode214 (e.g., electrode 214 may be tubular so that coolant can flow throughit). In other embodiments, the coolant flows around or adjacent theelectrode 214. For example, an outer member, illustrated as a conduit234 in FIG. 8, can surround the electrode 214 such that fluid can flowbetween the electrode 214 and the conduit 234. Additionally oralternatively, the ablation assembly 208 can be actively cooled orheated using one or more thermal devices (e.g., Peltier devices),cooling/heating channels, or the like.

Referring to FIGS. 8 and 9, the elongate shaft 230 extends from thecontrol module 210 to the ablation assembly 208 and includes a powerline lumen 320, a delivery lumen 324, and a return lumen 326. A powerline 280 extends through the power line lumen 320 and couples thecontroller 244 to the electrode 214. The delivery lumen 324 providesfluid communication between the fluid source 260 and the energy emitterassembly 220 and balloon 212. The return lumen 326 provides fluidcommunication between the balloon 212 and/or electrode 214 and the fluidreceptacle 262. The elongate shaft 230 can be made, in whole or in part,of one or more metals, alloys (e.g., steel alloys such as stainlesssteel), plastics, polymers, and combinations thereof, as well as otherbiocompatible materials, and can be flexible to pass conveniently alonghighly branched airways. Sensors can be embedded in the elongate shaft230 to detect the temperature of the fluids flowing therethrough.

Referring to FIGS. 10-12 in which the ablation assembly 208 is in anexpanded configuration, the conduit 234 surrounds and protects theelectrode 214 and the power line 280 from the external environment andfrom external forces which could cause connection failure. Theelectrical connections are also not exposed to bodily fluids. The powerline 380 can be routed along other fluid paths, if needed or desired.Alternatively, electrode 214 may be a metallic tubular member withconduit 234 being coupled to each of its ends in order to delivercoolant through the electrode 214. In this case, electrode 214 has anexposed external surface which is used to contact the airway wall duringenergy delivery.

The conduit 234 includes a proximal section 286, a distal section 288,and a non-linear section 300. The proximal section 286 functions as aninlet and extends distally from the elongate shaft 230. The non-linearsection 300 extends circumferentially about the balloon 212 and has anarc length in a range of about 180 degrees to 450 degrees. As shown inFIG. 11, in the expanded configuration of ablation assembly 208, atleast a portion of the non-linear section 300 can be positioned along animaginary plane 301 that is approximately perpendicular to alongitudinal axis 310 of the inflated balloon 212 (and catheter shaft230). The distal section 288 is aligned with the proximal section 286and functions as an outlet and extends distally to the atraumatic tip240.

When deflated (i.e., when not pressurized with coolant), the conduit 234can be highly flexible to conform about the elongate shaft 230 and canbe made, in whole or in part, of a material that assumes a preset shapewhen pressurized or activated. Such materials include, withoutlimitation, thermoformed polymers (e.g., polyethylene terephthalate,polyethylene, or polyurethanes), shape memory materials, or combinationsthereof. When the conduit 234 is inflated, it assumes a preset shapeconfigured to position electrode 214 in the desired transverseorientation with respect to longitudinal axis 310.

The balloon 212 can be made, in whole or in part, of polymers, plastics,silicon, rubber, polyethylene, polyvinyl chloride, chemically inertmaterials, non-toxic materials, electrically insulating materials,combinations thereof, or the like. To enhance heat transfer, the balloonsidewall can comprise one or more conductive materials with a highthermal conductivity. For example, conductive strips (e.g., metalstrips) can extend along the balloon 212 to help conduct thermal energyaway from hot spots, if any. The balloon 212 can conform toirregularities on the airway surface (e.g., cartilaginous rings, sidebranches, etc.) and can be made, in whole or in part, of a distensiblematerial, such as polyurethane (e.g., low durometer polyurethane) orother type of highly conformable material that may be transparent,semi-transparent, or opaque. The balloon 212 can have different inflatedshapes, including a hot dog shape, an ovoid shape, a cylindrical shape,or the like.

FIG. 13 shows the electrode 214 positioned in a channel 330 of theconduit 234 and includes a coolant channel 340. The electrode main body350 can be a rigid tube made, in whole or in part, of metal (e.g.,titanium 304, stainless steel, or the like) or other suitable metal. Insome embodiments, conduit 234 does not extend over the entire electrode214, leaving a central portion of the tubular electrode exposed fordirect contact with the airway wall. In other embodiments, the electrodemain body 350 is made, in whole or in part, of a shape memory material.Shape memory materials include, for example, shape memory metals oralloys (e.g., Nitinol), shape memory polymers, ferromagnetic materials,combinations thereof, and the like. These materials can assumepredefined shapes when released from a constrained condition ordifferent configurations when activated with heat. In some embodiments,the shape memory material can be transformed from a first presetconfiguration to a second preset configuration when activated (e.g.,thermally activated).

As shown in FIGS. 14 and 15, sensors 360 a, 360 b (collectively “360”)are coupled to the electrode main body 350. A pair of lines 370 a, 370 b(collectively “370”) pass through the channel 340 and are coupled to thesensors 360 a, 360 b, respectively. In some embodiments, the sensor 360a is a contact sensor, and the sensor 360 b is a temperature sensorand/or a pressure sensor. The number, positions, and types of sensorscan be selected based on the treatment to be performed.

In multilayer embodiments, the electrode main body 350 can include atleast one tube (e.g., a non-metal tube, a plastic tube, etc.) with oneor more films or coatings. The films or coatings can be made of metal,conductive polymers, or other suitable materials formed by a depositionprocess (e.g., a metal deposition process), coating process, etc., andcan comprise, in whole or in part, silver ink, silver epoxy,combinations thereof, or the like.

Radio-opaque markers or other types of visualization features can beused to position the main body 350. To increase visibility of theelectrode 214 itself, the electrode 214 may be made, in whole or inpart, of radiographically opaque material.

FIGS. 16-18 show one exemplary method of using the treatment system 200.A physician can visually inspect the airway 100 using the deliveryapparatus 206 to locate and evaluate the treatment site(s) andnon-targeted tissues before, during, and/or after performing a therapy.The delivery apparatus 206 can be a guide tube, a delivery sheath, abronchoscope, or an endoscope and can include one or more viewingdevices, such as optical viewing devices (e.g., cameras), optical trains(e.g., a set of lens), and the like. For example, the delivery apparatus206 can be a bronchoscope having one or more lights for illumination andoptical fibers for transmitting images. The catheter 207 may be adaptedto be delivered over a guidewire (not shown) that passes between theballoon 212 and the energy emitter assembly 220. This provides for rapidexchange capabilities.

When the delivery apparatus 206 of FIG. 16 is moved along a body lumen101 (e.g., airway), the collapsed ablation assembly 208 is held within aworking channel 386 of the delivery apparatus 206. The conduit 234 canform a loop 221 such that the electrode 214 is almost parallel to a longaxis 373 when the catheter 207 is in a substantially straightconfiguration. In the illustrated embodiment of FIG. 16, an angle β isdefined between the direction of the long axis 373 of the catheter 207and a long axis 374 of the electrode 214. The angle β can be in a rangeof about 0 degrees to about 30 degrees. In some embodiment, the angle βis in a range of about 0 degrees to about 20 degrees. The electrode 214,being curved, can also nest with and partially encircle the elongateshaft 230. In certain embodiments, at least a portion of the elongateshaft 230 is disposed within an arc of the electrode 214 for a furtherreduced profile. As such, the shaft 230 can be positioned between theends of the electrode 214. Electrode 214 may have various lengths,depending on the desired length of the lesion to be created in eachelectrode position. In preferred embodiments, electrode 214 has a lengthof at least about 2 mm up to about 3 mm. The electrode can have a width(or diameter if cylindrical) no larger than the width of the spacesbetween the cartilage rings, preferably in some embodiments being 0.1 toabout 3 mm.

With continued reference to FIG. 16, the diameter D_(L) of the workingchannel 386 can be less than about 8 mm. The diameter D_(B) of thedeflated balloon 212 can be relatively small. For example, a minimumdiameter D_(B min) can be in a range of about 2 mm to about 3 mm, and amaximum diameter D_(B max) in a range of about 5 mm to about 6 mm whenthe balloon 212 is fully collapsed. If the electrode 214 is collapsible,the diameter D_(max) of the ablation assembly 208 can be less than about3 mm. In ultra low-profile configurations, the maximum diameter D_(max)can be less than about 2.8 mm.

The balloon 212 can be inflated to move the energy emitter assembly 220near (e.g., proximate to or in contact with) the airway 100. The angle βcan be increased between 70 degrees and about 110 degrees when theballoon 212 is fully inflated. FIG. 17 shows the ablation assembly 208deployed, wherein the electrode 214 can be about perpendicular to thelong axis 373. There can be play between the energy emitter assembly 220and the balloon 212 such that the angle β is in a range of about 60degrees to about 120 degrees in order to accommodate variations ofanatomical structures, mis-alignment (e.g., mis-alignment of thecatheter shaft 230), or the like. In some embodiments, the electrode 214moves towards a circumferentially extending orientation as it moves froma delivery orientation to the deployed orientation. The electrode 214 inthe deployed orientation extends substantially circumferentially alongthe wall of the airway 100. In certain embodiments, the electrode 214will be configured to be positioned entirely within the spaces 374between cartilage rings 376 along the airway wall when the ablationassembly 208 is in the fully deployed configuration.

FIGS. 17 and 18 show the energy emitter assembly 220 fluidically coupledto both the elongate shaft 230 and the balloon 212. Generally, coolantcools the tissue-contacting portion 215 of the energy emitter assembly220. The cooling section 209 of the ablation assembly 208 contacts theairway wall 100 so as to cool tissue adjacent to the tissue-contactingportion 215 while energy is outputted by the electrode 214. The coolingsection 209 can be formed by the portions of the energy emittingassembly 220 and the balloon 212 that contact the airway wall 100.

As the balloon 212 inflates, the electrode 214 moves (e.g., pivots,rotates, displaces, etc.) from a first orientation of FIG. 16 in whichthe electrode 214 extends axially along the airway 100 and a secondorientation of FIG. 17 in which the entire electrode 214 is disposed ina space 374 between adjacent cartilage rings 376 a, 376 b. The balloon212 can both cool the airway 100 and cause the electrode 114 to seat inthe space 374.

FIG. 17 shows the energy emitter assembly 220 positioned to locate theelectrode 214 in the space 374. In certain embodiments, the electrode214, in the first orientation, extends a distance with respect to alongitudinal axis 373 (see FIG. 16) can be greater than the distance theelectrode 214, in the second orientation, extends with respect to thelongitudinal axis 373.

To deploy the energy emitting assembly 208, coolant from the elongateshaft 230 flows through the energy emitter assembly 220 and into theballoon 212. The electrode 214 can output a sufficient amount of energyto ablate a target region. The coolant absorbs thermal energy fromelectrode 214 and the airway wall 100.

The diameter D_(E) of the electrode 214 and conduit 234 can be in arange of about 1.5 mm to about 2.5 mm when pressurized with coolant.Such embodiments are well suited to treat tissue outside the lung alongthe main bronchi. In certain embodiments, the diameter D_(E) is about 2mm. In yet other embodiments, the diameter D_(E) can be in a range ofabout 0.1 mm to about 3 mm. The diameter D_(E) of the deflated conduit234 and electrode 214 can be about 0.1 mm to about 1 mm.

To treat a bronchial tree of a human, the diameter of the inflatedballoon 212 can be in a range of about 12 mm to about 18 mm. Forenhanced treatment flexibility, the inflated balloon diameter may be ina range of about 7 mm to about 25 mm. Of course, the balloon 212 can beother sizes to treat other organs or tissue of other animals.

The ablation assembly 208 provides differential cooling because thecoolant in the energy emitter assembly 220 is at a lower temperature andhigher velocity than the coolant in the balloon 212. Coolant,represented by arrows, flows out of the elongate shaft 230 and into theenergy emitter assembly 220. The coolant proceeds through the energyemitter assembly 220 and the coolant channel 340 (FIG. 15) of theelectrode 214. The coolant absorbs thermal energy from the electrode214. The heated coolant flows into the tip 240 and proceeds proximallythrough a lumen 400, as shown in FIG. 18. The coolant flows through avalve 420 (e.g., a throttle) and passes through a port 424. The valve420 is disposed along a fluid path connecting the energy emittingassembly 220 and the portion of the balloon 212 defining the coolingsection 209. The coolant circulates in a chamber 426 and absorbs heatfrom the tissue. This helps keep shallow tissue below a temperature thatwould cause cell death or tissue damage.

The coolant flows through a port 430, a lumen 432, and a throttle 434.The throttles 420, 434 can cooperate to maintain a desired pressure. Thethrottle 420 is configured to maintain a first flow rate of the coolantthrough the energy emitting assembly 220 and a second flow rate of thecoolant through the cooling section 209. The first flow rate can besignificantly different from the second flow rate.

The conduit 234 can assume a preset shape when pressurized. The valves420, 434 can cooperate to maintain the desired pressure within theballoon 212 within a range of about 5 psig to about 15 psig. Suchpressures are well suited to help push the electrode 214 betweencartilaginous rings. Other pressures can be selected based on thetreatment to be performed. The valves 420, 434 can be throttle valves,butterfly valves, check valves, duck bill valves, one-way valves, orother suitable valves.

When RF energy is transmitted to the electrode 214, the electrode 214outputs RF energy that travels through tissue. The RF energy can heattissue (e.g., superficial and deep tissue) of the airway wall while thecoolant cools the tissue (e.g., superficial tissues). The net effect ofthis superficial and deep heating by RF energy and superficial coolingby the circulating coolant is the concentration of heat in the outerlayers of the airway wall 100, as discussed in connection with FIGS. 6and 7. The temperature of the connective tissue can be higher than thetemperatures of the epithelium, stroma, and/or smooth muscle. Byexample, the temperature of the connective tissue can be sufficientlyhigh to cause damage to the nerve trunk tissue or other deep tissuewhile other non-targeted tissues of the airway are kept at a lowertemperature to prevent or limit damage to the non-targeted tissues.

Heat can be concentrated in one or more of the internal layers (e.g.,the stroma) of the airway wall or in the inner lining (e.g., theepithelium) of the airway wall. Furthermore, one or more of the vesselsof the bronchial artery branches may be within the lesion. The heatgenerated using the electrode 214 can be controlled such that bloodflowing through the bronchial artery branches protects those branchesfrom thermal injury while nerve trunk tissue is damaged, even if thenerve tissue is next to the artery branches. The catheter 207 canproduce relatively small regions of cell death. For example, a 2 mm to 3mm section of tissue in the middle of the airway wall 100 or along theouter surface of the airway wall 100 can be destroyed. By theappropriate application of power and the appropriate cooling, lesionscan be created at any desired depth.

A circumferential lesion can be formed around all or most of thecircumference of the airway wall 100 by ablating tissue while slowlyrotating the ablation assembly 208 or by positioning the ablationassembly 208 in a series of rotational positions at each of which energyis delivered for a desired time period. Some procedures form adjacentlesions that become contiguous and form a circumferential band all theway around the airway wall 100. In some embodiments, the entire loop 221(FIG. 17) can be an electrode. The loop 221 can be coated with aconductive material and can carry the electrode. A single procedure canproduce a circumferential lesion. After forming the lesion, coolantflowing into the balloon 212 can be stopped. The balloon 212 is deflatedcausing the energy emitter assembly 220 to recoil away from the airwaywall 100. The catheter 207 may be repositioned to treat other locationsor removed from the subject entirely.

If the user wants the coolant in the balloon 212 to be at a lowertemperature than the coolant in the energy emitter assembly 220, chilledcoolant can be delivered into the balloon 212 and then into the energyemitter assembly 220. FIGS. 19 and 20 show such a coolant flow. Lowtemperature coolant flowing through the elongate body 230 passes throughthe valve 434 and the port 430. The coolant circulates in the chamber426 and absorbs heat. The heated coolant flows through the valve 420 andproceeds through the energy emitter assembly 220 to cool the electrode214.

Airway cartilage rings or cartilage layers typically have asignificantly larger electrical resistance than airway soft tissue(e.g., smooth muscle or connective tissue). Airway cartilage impedesenergy flow (e.g., electrical radiofrequency current flow) and makes theformation of therapeutic lesions with radiofrequency electrical energyto affect airway nerve trunk(s) challenging when the electrode is nextto cartilage.

Positioners can facilitate positioning of the electrodes. Suchpositioners include, without limitation, bumps, bulges, protrusions,ribs or other features that help preferentially seat the electrode 214at a desired location, thus making it easy to perform the treatment orto verify correct positioning. FIGS. 21 and 22 show the energy emitterassembly capable of serving as an intercartilaginous positioner. Whenthe balloon 212 presses against the airway 100, the loop 221 moves alongthe balloon 212 to preferentially position the electrodes 214 betweencartilage rings 452 a, 452 b. The loop 221 protrudes outwardly from theballoon 212 a sufficient distance to ensure that the ablation assembly208 applies sufficient pressure to the airway wall to causeself-seating. The catheter can be moved back and forth to help positionthe electrodes 214 next to soft compliant tissue 453 in the space 453.The energy emitter assembly 220 can be configured to displace a distanceD_(o) (e.g., measured along a long axis 310), which is at least half ofthe distance D between the cartilage rings 452 a, 452 b. This ensuresthat the electrodes 214 can be positioned generally midway between thecartilage rings 452 a, 452 b.

The plurality of electrodes 214 can reduce both treatment time andprocedure complexity as compared to a catheter with a single electrode.This is because the multi-electrode catheter may have to be positioned asmaller number of times within a bronchial tree (or other hollow organ)as compared to single electrode catheters to produce a number of lesionsof a desired therapeutic size. Multi-electrode catheters can thusprecisely and accurately treat a user's respiratory system.

FIG. 23 shows an energy emitter assembly 500 that includes twoelectrodes 510 a, 510 b (collectively “510”) spaced apart from oneanother about a circumference of a balloon 520. The electrodes 510 a,510 b can be about 45 degrees to 210 degrees from another with respectto a long axis 511 of an ablation assembly 501. Other electrodepositions are possible. FIG. 24 shows an energy emitter assembly 530with three electrodes 540 a, 540 b, 540 c (collectively “540”)positioned about 60 degrees from one another. In these embodiments, eachelectrode may be coupled to separate power lines to allow forindependent control of each, or all electrodes may be coupled to thesame power line so as to be operated together. Further, a pair ofelectrodes may be operated in a bipolar manner, wherein one electrode ispositive and the other negative, with RF power being transmitted fromone to the other through the tissue.

Referring to FIGS. 25 and 26, a distal end 560 of an energy emitterassembly 552 is coupled to a tip 562. A proximal end 570 of the energyemitter assembly 552 is coupled to an elongate body 574. A centralsection, illustrated as a curved section 576, is not directly connectedto a balloon 554. This allows for a significant amount of movement of anelectrode 583 and convenient alignment with gaps between cartilage orother features.

When the balloon 554 is partially inflated (shown in FIG. 25), anarcuate section 580 of the central section 576 can be generallyperpendicular to a longitudinal axis 582 of the balloon 554. When theballoon 554 is fully expanded (shown in FIG. 26), there can besufficient clearance to allow movement of the electrode 583 withoutsignificant deformation of the balloon 554. For example, the electrode583 can be moved an angle α in a range of about −30 degrees to about 30degrees. Other angles are also possible.

FIGS. 27 and 28 show a conformable balloon 594 that can be made, inwhole or in part, of a highly compliant material. Highly compliantmaterials include, without limitation, silicon, rubber, polyethylene,polyvinyl chloride, or other materials capable of undergoing largedeformation. FIG. 29 shows a sidewall 595 of the balloon 594 contactingan airway wall 597 and providing a relatively high amount of surfacecontact. This provides rapid and effective cooling of tissue on and nearthe airway wall surface while a deeper target region 601, illustrated asa section of nerve tissue, is damaged.

FIGS. 30-32 show an ablation assembly 600 including an integral energyemitter assembly 610 with internal electrodes 620 a, 620 b. A generallyoutwardly protruding U-shaped portion 650 of a sidewall 630 can helpposition the electrodes 620 a, 620 b. An elongate body 670 extendsproximally from a balloon 640 and includes a delivery lumen 672, areturn lumen 674, and an interior support shaft 675. A port 679 providesfluid communication between a cooling channel 678 and a chamber 680. Thecoolant exits the balloon 640 via the return line 674. The sidewall 630forms a section of the delivery lumen 672. In some embodiments, conduits(e.g., fluid lines or hoses) provide fluid communication between theelongate body 670 and the energy emitter assembly 610.

FIGS. 33 and 34 show an ablation assembly 710 including an inflatableballoon 720 and an energy emitter assembly 730 (shown in dashed line inFIG. 34). Separate channels provide separate fluid paths toindependently adjust the pressure in the balloon 720 and energy emitterassembly 730. Both the balloon 720 and the energy emitter assembly 730can be made of a compliant material (e.g., urethane or other compliantbiocompatible material) to fit in differently sized bronchial lumens.Advantageously, fewer catheter stock keeping units (SKUs) can berequired compared to catheter balloons made from non-compliantmaterials, which are not optimally adjustable for fitting in differentsized lumens.

The catheter 704 has a proximal section 732 configured for differentialcooling. A proximal end 741 of an inflow line 742 has an inline valve743 and is in fluid communication with an inflow lumen 750 of FIG. 35. Afeed conduit 816 of FIGS. 37 and 38 delivers coolant from the inflowlumen 750 to a chamber 811 of the inflation assembly 780 a.

A proximal end 744 of an inflow line 745 of FIG. 33 has an inline valve746 and is in fluid communication with an inflow lumen 752 of FIG. 35.The inline valves 743, 746 can be connected to fluid supplies. Aproximal end 758 of an outflow line 759 has an outline valve 761 and isin fluid communication with an outflow lumen 756 of FIG. 35. Power lines760, 762 separately couple electrodes 790 a, 790 b respectively to apower source connector 781.

FIGS. 36 and 37 show inflatable ablation assemblies 780 a, 780 b(collectively “780”) in an expanded state. The assemblies 780 can beindependently inflated to help position electrodes 790 a, 790 b.Different coolants (e.g., saline, water, or the like) at differentcoolant temperatures (e.g., iced, warmed, room temperature, etc.) canflow through the ablation assemblies 780. The inflation pressure can beincreased to increase the force applied to an airway wall and to helpseat the ablation assemblies 780.

The ablation assemblies 780 may be spaced apart to allow each of theablation assemblies 780 to be positioned between cartilaginous rings.For example, the distance D in FIG. 36 can be in a range of about 1 mmto about 5 mm. A physician can determine the distance D by inspecting anairway and can then select an appropriately sized catheter. In additionto being axially spaced apart, electrodes 790 a, 790 b may be disposedin circumferentially offset positions so as to deliver energy todifferent facets of the airway wall. For example, electrode 790 a may beoffset by 45 degrees, 90 degrees, or 180 degrees relative to electrode790 b. Further, each ablation assembly 780 a, 780 b may have multipleelectrodes spaced circumferentially around balloon 720.

Fluids at different temperatures can be delivered to the ablationassemblies 780 and the balloon 720. In some embodiments, the coolant isdelivered through cooling channels of the energy emitting assemblies 780and then into the balloon 720 if the therapeutic goal is to producelesions with the maximum depth. The balloon 720 and the energy emittingassemblies 780 can also be coupled to a common source (or sink) path.This allows for unique coolant flow in each path. This also may reducethe overall diameter of the expanded ablation assembly 710 as comparedto using completely separate coolant paths. Electrodes 790 a, 790 b maybe independently controlled so that energy may be deliveredsimultaneously or separately, and at the same or different power levels.

FIGS. 39 and 40 show an ablation assembly 800 with a deployment catheter811 having a balloon 810 and an energy emitter assembly 820 removablypositionable over the balloon 810. Energy emitter assembly 820 comprisesa pair of tubular shafts 817, 819 connected by a distal loop 823. Distalloop 823 may be pre-formed around an axis parallel to the longitudinalaxes of the shafts 817, 819. Alternatively the distal loop 823 can beconfigured to assume the deployed orientation when pressurized by theintroduction of coolant in shafts 817, 819.

One of shafts 817, 819 is adapted to deliver coolant through loop 823while the other received coolant from the loop and returns it to theproximal end of the device. In FIG. 41, the shaft 817 delivers coolantto the balloon 810. The coolant exits the balloon 810 via the shaft 819.As shown in FIG. 40, a distal tip 834 of deployment catheter 811 can beinserted and passed through a receiving opening 830 of the energyemitter assembly 820. Once an electrode, illustrated as a surfacemounted electrode 836, is positioned between the distal tip 834 and aproximal end 840 of the balloon 810, the balloon 810 is inflated tosnugly hold the energy emitter assembly 820.

The energy emitter assembly 820 can be moveable between a straightenedand collapsed configuration for delivery and the illustrated deployedconfiguration. For example, in the preshaped embodiment described above,the distal loop 823 on energy emitter assembly 820 can be straightenedand collapsed inwardly so as to be positionable in a constraining sheathduring introduction. Upon removal from the sheath, distal loop 823 willreturn to its unbiased deployed orientation, lying in a plane generallyperpendicular to the longitudinal axes of shafts 817, 819. Inalternative embodiments, the distal loop 823 may be flaccid andcollapsible when unpressurized, and will assume the desired deployedshape when coolant is introduced through shafts 817, 819. To manufacturedistal loop 823, a polymer tube may be heat treated to assume a desiredshape when pressurized.

By decoupling the energy emitter apparatus 820 from the deploymentcatheter 811 they may be introduced separately from each other, allowingthe apparatus to be introduced through very small-diameter passageways.This is particularly useful to allow the ablation assembly to beinserted through a working channel of a bronchoscope. First, the energyemitter assembly 820 may be collapsed and introduced through the workingchannel (with or without a sheath), then the deployment catheter 811 maybe introduced. The combined apparatus may then be assembled within theairway.

As shown in FIGS. 41 and 42, fluids can be independently deliveredthrough the energy emitter assembly 820 and the balloon 810. FIG. 41shows arrows representing coolant flowing through the energy emitterassembly 820. FIG. 42 shows arrows representing coolant flowing throughthe balloon 810. The coolant can flow through a delivery lumen 854 and aport 856. The coolant exits a chamber 857 via a port 860 and flowsthrough a return lumen 864. A separate delivery lumen 867 deliverscoolant to the energy emitter assembly 820. A return lumen 869 deliversthe coolant out of the energy emitter assembly 820. In some embodiments,coolants are independently delivered to the balloon 810 and the energyemitter assembly 820. Separate lines can be connected to the balloon 810and the energy emitter assembly 820.

One or move valves can provide for different flow rates through theballoon 810 and the energy emitter assembly 820. For example, a valvesystem (e.g., one or more valves, throttles, etc.) can provide a firstflow rate of coolant through the energy emitting assembly 220 and asecond flow rate of coolant through the balloon 810. The first flow ratecan be significantly different from the second flow rate. For example,the first flow rate can be significantly greater than the second flowrate. In yet other embodiments, the first flow rate can be generally thesame as the second flow rate.

Referring to FIGS. 43-45, a catheter 883 can provide ventilation duringablation treatment of an airway. An expandable element 882 has a distalend 884, a proximal end 886, and a ventilation passageway 890 extendingbetween the ends 884, 886. The expandable element 882 can be adouble-walled cylindrical balloon defining a cylindrical chamber betweenits inner and outer walls. The spacing between the inner and outer wallst (see FIG. 45) can be sufficiently large to permit enough fluid tocirculate in the element 882 to expand the energy emitting assembly 896into engagement with the airway wall and to effectively control tissuetemperatures.

The ventilation passageway 890 is configured to allow expiratoryairflow, represented by arrows 892 in FIG. 43, and inspiratory airflow,represented by arrows 894 in FIG. 44. A flow velocity sensor can bepositioned along the passageway 890 to determine changes in air flow dueto the treatment. Additionally or alternatively, a valve (e.g., aone-way valve, a two-way valve, etc.) or flow regulator can be used tocontrol air flow. Such elements can be installed in the passageway 890.

As in the embodiment of FIGS. 39-42, the energy emitter assembly 896 andthe expandable element 882 may be independently deployable. The energyemitter assembly 896 can be inflated from a delivery configuration(e.g., a straight configuration) to the illustrated treatmentconfiguration (illustrated as a loop). The expandable element 882 can beinflated to the illustrated tubular configuration. The inflated ends884, 886 can press against the airway to securely hold the electrode 900stationary with respect to the expandable element 882. A coolant cancirculate through an energy emitter assembly 896 and into the inflatableelement 882. For enhanced differential cooling, different coolants canflow through the energy emitter assembly 896 and the inflatable element882.

FIG. 46 shows an ablation assembly 910 with a coiled energy emitterassembly 920. Coolant flows through a delivery line 944 and a coiledsection 946. The coolant absorbs thermal energy from tissue near thecoiled section 946. The coolant also cools the electrode 940. Thecoolant flows to a distal end of the ablation assembly 910 and returnsproximally via a return line 950. The delivery line 944 and the returnline 950 form the catheter shaft 952. In this manner, both the airwaywall and the electrode 940 are simultaneously cooled without utilizing aseparate balloon.

The coiled section 946 can be formed of a hollow tubular member and hasseven coil turns. The number of coil turns can be increased or decreasedto increase or decrease the axial length of the coiled section 946. Eachcoil turn can be connected to an adjacent coil turn to preventseparation. Alternatively, adjacent coil turns may not be physicallycoupled together to allow the ablation assembly 910 to uncoil fordelivery through airways.

The ablation assembly 910 can be inflated to assume the coiledconfiguration and can be made, in whole or in part, of a pre-formedmaterial, such as PET or other thermoformed material. Alternatively, theablation assembly 910 can be formed of shape memory material thatassumes different configurations when thermally activated or whenreleased from a constrained configuration.

To help facilitate contact between the electrode 940 and tissue, theelectrode 940 can protrude outwardly. The electrode 940 can be a surfacemounted plate. In other embodiments, the electrode 940 is a conductivecoating.

FIG. 47 shows a coiled section 962 having a tubular member 964 withthree coil turns. The central coil turn 970 can be slightly larger thanthe adjacent coils 972, 974, such that an electrode 975 is positionedradially outward of the coils. Coolant can flow through a delivery line967, through the coiled section 962, and return via a return line 966.In some embodiments, an inner coil pushes the coil turn 970 outwardly.

FIGS. 48 and 49 show an open cooling channel in communication with achamber of a balloon. An electrode 1010 is mounted to the exterior ofballoon 1014. An annular rib 1030 can be formed in the wall of balloon1014, and the electrode 1010 may have a curved cross-sectional shapewhich nests over the annular rib to help maintain the position ofelectrode 1010 and to create greater surface area for heat transferbetween the balloon and the electrode. Coolant can be delivered througha delivery lumen 1016. The coolant passes through a port 1019 into achamber 1020 of a balloon 1014. The port 1019 is configured to directthe coolant towards the electrode 1010 in the form of a stream or sprayto cool the electrode. The coolant circulates and exits the chamber 1020via a port 1022. The coolant flows proximally along a return lumen 1018.To enhance cooling capabilities, the flow of coolant is aimed anddelivered towards the electrode 1010.

As shown in FIG. 50, a delivery conduit 1044 has a tip 1040 that extendslaterally away from a longitudinal axis 1050 towards the electrode 1010such that an outlet port 1042 is positioned in close proximity toelectrode 1010. Coolant can exit the port 1042 and flow directly towardelectrode 1010 to maximize cooling thereof.

FIG. 51 shows a deflectable delivery conduit 1110 of an elongate body1111 movable from a delivery position 1112 to a deployed position 1113of FIG. 52. The delivery conduit is resiliently biased into the deployedposition 1113. A deflated balloon 1130 can hold the delivery conduit1110 in the straight configuration until the balloon 1130 is inflated.Both the balloon 1130 and the biased delivery conduit 1110 can bedeployed together. In other embodiments, the delivery conduit 1110 ismade of a shape memory material that moves when activated. For example,the delivery conduit 1110 can move from the delivery position 1112 tothe deployed position 1113 when heated.

With reference to FIG. 53, the port 1114 is closer to a cooling channel1119 than to a longitudinal axis 1117 (FIG. 52). A fluid jet flows outof the port 1114 and into the channel 1119. The coolant can flow alongthe entire length and width of the electrode 1120 to provide generallyuniform electrode cooling. When the balloon 1130 is deflated, thedelivery conduit 1110 is moved back to a generally midline position.

FIGS. 54 and 55 show a portion of an energy emitter assembly 1200 thatincludes an internal electrode 1210 in an outer member or conduit 1220.Spacers 1222 a, 1222 b, 1222 c, 1222 d, 1222 e, 1222 f (collectively“1222”) space the electrode 1210 from the outer member 1220. Theelectrode 1210 has an inner cooling channel 1234. An outer coolingchannel 1235 is between the electrode 1210 and the outer member 1220. Asshown in FIG. 55, a coolant can flow in one direction through thecooling channel 1234 and a coolant can flow in the opposite directionthrough channel 1235.

FIGS. 56 and 57 show an electrode 1240 that has a plurality of coolingchannels 1242 a, 1242 b, 1242 c, 1242 d, 1242 e (collectively “1242”).The same fluid can be delivered through all of the channels 1242.Alternatively, different fluids at different temperatures can bedelivered through the channels 1242. In some embodiments, coolant flowsthrough some of the channels 1242 in one direction and a differentcoolant can flow through other channels 1242 in the opposite direction.

With reference to FIGS. 58 and 59, an electrode 1300 comprises a metaltube. Heat can be conducted about the circumference of the electrode1300 and into the coolant in a cooling channel 1320. The flow of heat isshown in FIG. 59. Heat can be generally uniformly transferred along thewall of the electrode 1300 so that heat is absorbed by the coolantflowing along the interior surface 1330.

Electrodes can include one or more heat transfer elements for enhancingheat transfer. FIG. 58 shows an optional heat transfer element in theform of a fin 1306, illustrated in dashed line, extending into thecoolant channel 1320. Any number of inwardly extending fins can belocated in the coolant channel 1320 for enhanced heat transfer viaconvention. The fins can be made of a material that has a high thermalconductivity. Other types of heat transfer elements or features (e.g.,surface texturing) can be used to control heat transfer.

FIGS. 60 and 61 show an electrode 1350 that has a thermally conductiveportion 1360 and an insulating portion 1362. The thermally conductiveportion 1360 can be made, in whole or in part, of metal or othermaterial with a high thermal conductivity. The insulating portion 1362can be made of an insulating material, such as rubber, plastic, or thelike. As shown in FIG. 61, heat transfer is generally isolated to thethermally conductive portion 1360 to prevent excessive heating of theinsulating member 1362, which may be in contact with a temperaturesensitive element, such as a balloon.

If electrodes have sharp edges at one or both ends, electrons have atendency to accumulate near those sharp edges and other irregularities.The voltage near the edges is often higher than in other regions of theelectrode. FIG. 62 shows an electrode 1370 connected to an insulatingmember 1372, and an applied charge, represented by plus signs, tends toaccumulate along the sharp edge 1374. The high charge causes excessiveheating and is referred to as an “edge effect.” When the highly chargededge 1374 contacts tissue, the high regional voltage near the electrodeedge 1374 results in more power being delivered to the tissue contactingor proximate to the edge 1374. Thus, that tissue becomes hotter thanother tissue contacting the electrode 1370. This results in non-uniformheating of the tissue and unwanted hot spots. During RF ablation, lesionformation can be very uneven and excessive tissue damage, and iscommonly referred to as edge effects.

FIG. 63 shows an electrode 1375 connected to an insulator 1376. Theelectrode 1375 is formed of a plurality of individual electrodes. One ormore of the individual electrodes may have sharp edges, but theelectrodes are sufficiently small such that the charge density isrelatively uniform across the length and breadth of the overallelectrode 1375. The charges are generally evenly distributed tominimize, limit, or substantially eliminate edge effects. This resultsin generally uniform temperatures along the length of the electrode1375, as shown in FIG. 63.

FIG. 64 shows a plurality of discrete spaced apart electrode elements,illustrated as electrode rings 1382 a, 1382 b, 1382 c, 1382 d(collectively “1382”). Each electrode ring 1382 comprises a plurality ofindividual electrodes to mitigate edge effects. Insulating portions 1390a, 1390 b, 1390 c, 1390 d (collectively “1390”) insulate the electroderings 1382.

FIG. 65 shows an edge 1430 of an electrode element 1410 covered byshielding 1420. An exposed contact surface 1440 of the electrode element1410 can contact tissue 1450 and can result in generally uniformheating. The shielding 1420 can be an insulating material that inhibitsor blocks energy outputted by the electrode element 1410. If theelectrode element 1410 outputs electrical energy, the shielding 1420 canbe made of an electrically insulating material, such as non-conductiveplastic or polymer or other dielectric material.

FIG. 66 shows an ablation assembly 1470 that includes an electrode 1480and shielding portions 1484 a, 1484 b (collectively “1484”). Theelectrode 1480 has a first end 1481, a second end 1483, and a main body1485. Shielding portions 1484 a, 1484 b cover the ends 1481, 1483 andcan be part of an ablation energy insulator. A generally uniformtemperature distribution can be produced along a length of the exposedelectrode 1480. The length of overlap between the electrode 1480 and theshielding portions 1484 can be selected based on the application. Insome embodiments, a length of about 4 mm of the electrode 1480 can bereceived within each of the shielding portions 1484. The length of theexposed section of the electrode 1480 can be in the range of about 6 mmto 10 mm. The length of the electrode 1480 can be about 8 mm. Otherdimensions are also possible.

The shielding portions 1484 a, 1484 b can be cooling conduits. Coolantcan flow through the shielding portions 1484 and through a coolingchannel of the electrode 1480. In other embodiments, a Peltier device isused to cool the electrode 1480. It will be understood that any of theelectrode embodiments of FIGS. 54-66 may be utilized in any of theenergy emitter assemblies disclosed in this application.

Lesion shapes can be controlled by adjusting the temperature of thecoolant, coolant flow rates, heat carrying capacity of coolants, thermalcharacteristics of the balloon (e.g., the heat transfer properties ofthe balloon), or the amount of delivered power. FIGS. 67A-71B showtemperature profiles and corresponding lesions formed by progressivelyincreased cooling by a balloon. The cooling capacity of the balloon canbe increased by decreasing the coolant temperature or by increasing thecoolant flow rate, or both. Lesion shaping can also be achieved byholding the cooling capacity of the balloon generally constant whilevarying the coolant capacity of the electrode or by increasing ordecreasing the power delivered to the tissue. By way of example, theablation assembly 208 in FIG. 8 can be used to form the lesions of FIGS.67B, 68B, 69B, 70B, and 71B. Because the balloon 212 has a largerdiameter than the electrode channel 340, there is a relatively low flowvelocity along the balloon surface as compared to the high velocity lowvelocity through the electrode 214. This results in differentialcooling. If the electrode 214 and the balloon 212 have independentflows, the coolants can be at different temperatures and/or flowvelocities for differential cooling. The ablation assembly 800 of FIGS.39-42 can be used for differential cooling. The power delivered by theelectrode 836 to the tissue can be fixed. The coolant flow rate throughthe energy emitter assembly 820 can be fixed. The coolant flow ratethrough the balloon 810 can be varied to form lesions of differentshapes.

FIG. 67A shows isotherms and temperature distributions in tissue, withisotherms of 80° C., 60° C., and 40° C. FIG. 67B shows a lesion 1504corresponding to the isotherms of FIG. 67A. The coolant in a coolingchannel 1522 is the only coolant that absorbs a significant amount ofheat. A balloon 1510 does not absorb a significant amount of thermalenergy and can be filled with fluid at a temperature that is generallyequal to room temperature or within a range of about 20° C.-30° C. Insome embodiments, the balloon 1510 is inflated with ambient air and canhold an electrode 1524 against the tissue 1500. In other embodiments,the balloon 1510 is inflated with warm saline.

FIG. 67B shows the lesion 1504 having a generally semicircular shape.The radius r and depth D can be increased or decreased by decreasing orincreasing, respectively, the temperature of the coolant in the coolingchannel 1522. Additionally or alternatively, the radius r and depth Dcan be increased or decreased by decreasing or increasing, respectively,the flow rate of the coolant.

Chilled coolant can be delivered through the balloon 1510 to reduce thecross-sectional width of the lesion at the tissue surface 1525. FIGS.68A and 68B show isotherms and a corresponding lesion 1527 when acoolant cools the electrode 1524 and when a low temperature coolantflows at a low velocity through the balloon 1510. The coolant in theballoon 1510 absorbs a sufficient amount of thermal energy to protecttissue that contacts or is proximate to the balloon-tissue interface.

The lesion can have a generally elliptical shape. In some embodiments,including the illustrated embodiment of FIG. 68B, the cross-sectionalwidth of the lesion 1504 at the surface 1525 is less than across-sectional width of the lesion 1504 of FIG. 67B at the surface1525. The cross-sectional width of the lesion 1504 of FIG. 68B increaseswith depth to a maximum width W_(Max) and then decreases to the deepestregion 1530. The maximum width W_(Max) is less than the depth D of thelesion 1504. FIG. 68B shows the lesion 1527 at the surface 1525 having awidth that is no more than about 150% of the electrode width. FIG. 69Bshows a maximum cross-sectional width of the lesion 1527 at the tissuesurface 1525 that is about equal to the electrode width.

FIGS. 69A and 69B show isotherms and a lesion 1527 when a lowtemperature coolant flows at a high velocity through the balloon 1510 ora very low temperature coolant flows at a low velocity through theballoon 1510. The somewhat teardrop shaped lesion 1527 extends from thetissue surface 1525. The width of a shallow or narrowed portion 1534 ofthe lesion 1527 is about equal to the cross-sectional width W_(E) of theelectrode 1524. Thus, the lesion 1527 at the surface 1525 has a maximumcross-sectional width that is no more than about 150% of anelectrode-tissue interface. This ensures that a minimal amount ofsurface tissue is damaged. The lesion 1527 tapers outwardly from theshallow portion 1534 to an enlarged region 1535. The lesioncross-sectional width gradually increases with depth to a maximum widthW_(Max). The maximum width W_(Max) can be more than about 1 to about 3times the cross-sectional width at the surface 1525. The deepest region1530 of the lesion 1527 has a partially circular shape.

FIGS. 70A and 70B show isotherms and a teardrop shaped lesion 1527 thatcan be formed when a very low temperature coolant flows at a highvelocity through the balloon 1510. The lesion 1527 extends from thetissue surface 1525 and has a narrow shallow region 1534 that rapidlyexpands outwardly to a wide deep region 1552. The width of the shallowportion 1534 is less than a width W_(E) of the electrode 1524. Thecross-sectional width rapidly increases with depth to a maximum widthW_(Max). Thus, most of the volume of the lesion 1527 is deep in thetissue. As such, the depth of the centroid of area is significantlygreater than the width of the lesion 1527 at the surface 1525.

FIGS. 71A and 71B show isotherms and a corresponding circular shapedlesion 1527 that can be formed when a very low temperature coolant flowsat a very high velocity through the balloon 1510. The lesion 1527 isdisposed at a depth D from the tissue surface 1525. The maximumcross-section width W_(Max) of the lesion 1527 is at a depthD_(Width Max). The lesion 1527 is spaced apart from the electrode-tissueinterface and can have different shapes depending on the flow rates andthe temperatures of the coolants. Differential cooling can be used toachieve other buried lesion shapes, such as generally elliptical shapes,elongated shapes, or the like.

The D_(Width Max) can be selected based on the location of the targetregion. To damage nerve tissue, the D_(Width Max) can be at least about2 mm to ensure that the lesion includes the nerve tissue. The depth Dcan be at least about 2 mm to mitigate or avoid a significant amount ofdamage to smooth muscle tissue. Such embodiments are well suited fortreating an airway wall because the smooth muscle tissue is typicallynot below a depth of 2 mm. In this manner, the cross-sectional width ofthe target region can be maximized at a depth deeper than the smoothmuscle tissue. The majority, and in some embodiments substantially all,of the lesion will be in tissue which is not smooth muscle tissue,typically lying deeper in the airway wall than the region of smoothmuscle tissue. Further, any damage to smooth muscle cells in the airwaywall can be less than the amount of damage that, in the absence ofdamaging nerve tissue, would be required to substantially alter theresponsiveness or constriction of the airway, e.g. as a result ofasthma, COPD, or other pulmonary disease.

The lesion can be separated from the tissue surface by a protectedregion in which a significant amount of the tissue is not permanentlydamaged. FIGS. 70B and 71B show a protected region 1561 having a depthD. Advantageously, because a significant amount of tissue in theprotected region 1561 is not permanently damaged, tissue functioning canbe preserved. The depth D_(P) can be at least about 1 mm to about 2 mmto ablate nerve tissue.

It will be understood that the term “lesion” as used herein is intendedto mean tissue which is permanently damaged, i.e. to the point of celldeath. In some cases, the delivery of energy will cause temporary ornon-lethal damage to cells outside the region referred to as the“lesion.” For example, epithelial or smooth muscle cells may betemporarily damaged or altered by the energy delivery described herein.However, advantageously, through the use of differential cooling, thesecells can recover and remain functional, thus are not considered part ofthe “lesion” created. By contrast, the catheter 207 can impart permanentdamage to nerve tissues lying deep in the airway wall or on the outsideof the airway wall, thus attenuating nerve signals that are the cause ofcertain pulmonary diseases.

The catheter 207 of FIG. 8 can form the lesion 1527 of FIG. 71B. Thedelivery lumen 324, return lumen 326, and electrode channel 340 (FIG.13) can each have a diameter of about 2.1 mm. The balloon 212 can bemade of a low durometer urethane with a wall thickness of about 0.019 mmto about 0.025 mm and a longitudinal length of about 20 mm. The outerdiameter of the balloon 212 is about 16 mm and is inflated to a pressureof about 10 psig. Coolant flows through the electrode 214 at a flow rateof about 100-120 ml/min and is chilled saline or water (e.g., ice coldsaline or water). The electrode 214 has a length of about 8 mm anddelivers about 25 W of power to the tissue to form the lesion 1527 witha maximal depth D_(Max) of about 7 mm to about 8 mm and the protectionregion 1561 having a D_(P) of about 1 mm to about 2 mm. In other words,the lesion 1527 is spaced apart a distance at least 1 mm to about 2 mmfrom the tissue surface.

FIGS. 72 and 73 show a delivery device 1600 with an electrode 1610 andan expandable element in the form of a balloon 1620. The electrode 1610extends distally from the deflated balloon 1620, which can closelysurround an elongate shaft 1640. A distal section 1688 of the elongateshaft 1640 extends axially through a chamber 1690 and carries theelectrode 1610. The balloon 1620 is distensible distally to extend alongthe electrode 1610 when inflated.

FIG. 74 shows an inflated generally bell shaped balloon 1620 thatdefines a distally facing contact surface 1630. The contact surface 1630surrounds the electrode 1610 and has a generally annular shape. Theballoon 1620 can prevent external fluid flow from flowing along theelectrode 1610.

FIG. 75 shows coolant flowing along a delivery line 1700. The coolantexits an outlet 1710 and flows along an inner surface 1720 of theelectrode 1610. The coolant is heated as it absorbs thermal energy. Thecoolant exits the electrode 1610 via ports 1720 a, 1720 b and circulatesin a balloon chamber 1690. The coolant absorbs thermal energy to cooltissue. The coolant exits the chamber 1690 via ports 1730 a, 1730 b andflows through a return line 1740.

If external liquid (e.g., blood, urine, mucous, etc.) flows about thedelivery device 1600, the balloon 1620 can block liquid flow along thetissue 1650. The electrode 1610 can deliver energy to the tissue 1650without an appreciable amount of heat being absorbed by the externalfluid flow. For example, if the tissue 1650 is cardiac tissue, theballoon 1620 can prevent a significant amount of blood flow between theballoon 1620 and the tissue 1650, thus preventing tissue near theelectrode 1610 from being cooled due to blood flow. Additionally, theballoon 1620 can cool the tissue 1650 to shape lesions, if needed ordesired.

FIGS. 77-81 show a delivery device 1800 having an electrode 1810 and abell-shaped expandable element 1814 coupled to a coaxial shaft 1801. Theelectrode 1810 is coupled to a distal face of expandable element 1814.An inner lumen 1803 in shaft 1820 delivers cooled inflation fluid to theinterior of expandable element 1814 for the expansion thereof. Inflationfluid flows out from expandable element into outer lumen 1850 in shaft1852. Coolant can flow out of the port 1818 towards a proximal electrodesurface 1830 and can circulate through a chamber 1840. Electrode 1810may be coupled to power wires (not shown), which may extend through thefluid delivery lumen and balloon, to deliver energy to the electrode.Alternatively, a cryogenic fluid may be circulated through the balloonto cool the electrode to cryogenic temperatures to perform cryogenicablation.

FIGS. 82-86 show a delivery device 1900. A fluid for inflating anexpandable element 1910 flows along a delivery lumen 1920 and into achamber 1930. The fluid exits via a return lumen 1934. Coolant thatcools an electrode 1940 flows along delivery lumen 1950 and circulatesthrough an electrode chamber 1954. The coolant exits the chamber 1954via a return lumen 1960. The electrode coolant and the balloon coolantcan be at different temperatures for differential cooling.Advantageously, the flow rates and temperatures of the electrode andballoon coolants can be independently controlled.

The distally ablating delivery devices of FIGS. 72-86 are especiallywell suited to deliver energy to cardiac tissue. The balloons can befilled with a gas such a carbon dioxide, helium, or air or other fluidwith relatively low heat capacity to form endocardial surface lesions,even relatively large endocardial surface lesions. The fluid can be at atemperature that is generally equal to or greater than the normaltemperature of the tissue to prevent unwanted cooling. A low temperaturecoolant can pass through the balloons to protect and cool the tissuenear the balloon-tissue interface to limit or eliminate endocardiallesion size and can be used to produce relatively large epicardiallesions.

FIGS. 87A-89B show isotherms and corresponding legions. FIG. 87A showsan electrode 1610 delivering energy to tissue 2010. The electrode 1610can be cooled using a coolant. If the tissue 2010 is cardiac tissue,blood can flow across a tissue surface 2034 and can absorb heat from thetissue 2010 via convection. Accordingly, natural body functioning canhelp cool the tissue 2010 to form a lesion 2030 with a shape that issimilar to the shape of the lesion 1527 in FIG. 68B. The maximal depthD_(Max) of FIG. 87A can be less than the thickness t to avoid damagingthe epicardium 2032, but a section of the endocardium 2034 near theelectrode 1610 is damaged.

The balloon 1620 can be inflated with a gas (e.g., ambient air) or otherfluid that does not absorb a significant amount of thermal energy. Theballoon 1620 blocks blood flow and allows ablation of the tissueadjacent to the balloon-tissue interface 2042. As shown in FIG. 88B, thelesion 2030 has a wide base. Thus, the maximum width of the lesion 2030of FIG. 88B located along the surface 2044.

Chilled coolant can be passed through both the electrode 1610 and theballoon 1620 to form lesions spaced apart from the deliverydevice-tissue interface.

FIGS. 89A and 89B show isotherms and a corresponding lesion 2030. Acoolant can cool the electrode 1610. A coolant can pass through theballoon 1620 to keep tissue proximate to the balloon 1620 at or below atemperature that induces cell damage or death. The endocardium 2034 canbe protected and a significant amount of the epicardium 2032 can bedamaged. A protected region 2035 is between the lesion 2030 and theelectrode 1610.

Other types of structures can block fluid or blood flow. For example,shields, masks, umbrella structures, or the like can be placed againsttissue to prevent the flow of natural bodily fluids along the tissueand, thus, promote shallow lesion formation.

FIGS. 90 and 91 show a non-inflatable delivery device 2100 having anelectrode 2110 with discharge ports 2112. Advantageously, lesions can beformed without expanding the delivery device 2100. The ports 2112 arecircumferentially spaced apart from one another and are configured tospray the coolant towards the tissue 2116. Coolant, represented byarrows, flows out of the ports 2112 and along the tissue 2116. A sprayangle α between a longitudinal axis 2117 and the spray can be less thanabout 90 degrees. In certain embodiments, the spray angle α is less thanabout 70 degrees to ensure that the coolant absorbs a significant amountof heat via convection.

The coolant can be chilled saline or chilled water, which mixes withbodily fluids (e.g., blood). If the delivery device 2100 is used inorgans containing air or other gas, the coolant can be a gas.

FIG. 92 shows a modified delivery device 2020 that has a first set ofcircumferentially spaced discharge ports 2021 and a second set ofcircumferentially spaced discharge ports 2022. The sets of ports 2021,2022 are axially spaced apart from one another along a longitudinal axis2028 of the delivery device 2020.

FIGS. 93 and 94 show a delivery device 2031 that includes a pressurereducing element 2032 for producing a low temperature fluid. A fluid canflow down a delivery lumen 2037 of an elongate body 2039. The fluidpasses through the pressure reducing element 2032 to form a lowtemperature fluid within the electrode chamber 2039. As used herein, theterm “pressure reducing element” refers, without limitation, to a deviceconfigured to reduce the pressure of a working fluid. In someembodiments, the pressure reducing element can reduce the pressure ofthe working fluid to a pressure equal to or less than a vaporizationpressure of the working fluid. The working fluid can comprise arefrigerant (e.g., a cryogenic refrigerant or a non-cryogenicrefrigerant). In some embodiments, the pressure reducing elements are inthe form of pressure reduction or expansion valves that causevaporization of at least a portion of the working fluid passingtherethrough. The pressure reducing element vaporizes an effectiveamount of the working fluid (e.g., a cryogenic fluid) to reduce thetemperature of the working fluid. In some modes, substantially all ormost of the working fluid by weight passing through the valve element2032 is converted to a low temperature and low pressure gas. The lowtemperature gas flows through the expansion chamber 2039 and exits viathe discharge vents 2033. In some embodiments, the pressure reducingelement 2032 can be a nozzle valve, a needle valve, a Joule-Thomsonthrottle, a throttle element, or any other suitable valve for providinga desired pressure drop. For example, a Joule-Thomson throttle canrecover work energy from the expansion of the fluid resulting in a lowerdownstream temperature. In some embodiments, the pressure reducingelements can be substituted with flow regulating elements (e.g., a valvesystem) especially if the working fluid is a non-refrigerant, such aswater.

A high pressure gas P₁ of FIG. 94 is passed through the delivery lumen2037. The high pressure gas P₁ passes through the element 2032 andenters the expansion chamber 2039 where the pressure drops to P₂. Thedrop in pressure from P₁ to P₂ leads to a drop in temperature of the gasfrom T₁ to T₂. The magnitude of the temperature change is given by:

T ₁ −T ₂=μ(P ₁ −P ₂)

where

-   -   T is the temperature of the gas;    -   P is the pressure of the gas;    -   μ is the is the Joule-Thomson coefficient of the gas;    -   Subscript 1 denotes a high pressure condition; and    -   Subscript 2 denotes a low pressure condition.

A second pressure drop occurs when the gas in the expansion chamber 2039exits through the ports 2033 and drops to a surround pressure. If thedelivery device 2031 is used in the lung, the surrounding pressure isatmospheric pressure. This temperature drop is:

T ₂ −T ₃=μ(P ₂ −P _(ATM))

Thus, the cold gas flowing into the expansion chamber 2039 through thevalve element 2032 will cool the electrode 2035 and the cold gas flowingfrom the expansion chamber 2039 through the ports 2033 can be directedat the surrounding airway and will cool the surrounding tissue.

The Joule-Thomson coefficient (p) is specific for each gas orcombination of gasses. Standard temperature values for u are:

Carbon Dioxide

$\mu_{{CO}_{2}} = {1.16 \times 10^{- 5}\frac{K}{Pa}}$

Air

$\mu_{air} = {0.23 \times 10^{- 5}{\frac{K}{Pa}.}}$

These coefficients indicate that for a given pressure drop, CO₂ willcause a 5 times greater drop in temperature than a similar drop inpressure experienced by air.

The use of air in the lungs can be desirable. Carbon dioxide can be usedif the flow rates of coolant gas are sufficiently low so as to notoverwhelm the patient's ability to ventilate this additional carbondioxide out of the lungs. The cooling effect can be enhanced if thecoolant in the coolant conduit is a high pressure liquid, such as liquidair or liquid CO₂. The high pressure liquid passes through the pressurereducing element 2032 (e.g., a throttle) and undergoes an endothermalphase change from a high pressure liquid to a high pressure gas, whichcauses the temperature of the gas to be lower than that of the highpressure liquid. It then goes through a Joule-Thomson expansion from P₁to P₂ which causes a further drop in temperature, before being ventedout of the electrode via the vents 2033.

It will be understood that in any of the embodiments of energy emitterassemblies disclosed herein, the electrodes and/or the tissue adjacentto the electrodes may be cooled by fluids undergoing Joule-Thomsonexpansion as described above. For example, a pressurized fluid may bepassed through a pressure reducing element in any of these energyemitting assemblies such that the fluid undergoes a phase change to gas,which may be vented directly toward the electrodes to be cooled, and/ortoward the airway wall tissues adjacent to the area of contact by theelectrodes.

FIGS. 95-97 show an actuatable catheter 2200 movable from a deliveryconfiguration of FIG. 95 to a tissue treatment configuration of FIG. 96.The actuatable catheter 2200 includes a sleeve 2210 and an elongate body2212. The elongate body 2212 includes an electrode 2214 with ports,illustrated as three vents 2215. A coolant, which may be a lowtemperature liquid such as chilled saline or water, can be dischargedvia the vents 2215. A valve element 2216 (e.g., a Joule-Thomson element)can reduce the temperature of the working fluid.

The deployed section 2230 can have an arcuate shape for conforming tothe inner surface of an airway or other vessel. The arcuate deployedsection 2230 can have an axis of curvature which is generally coplanarwith a longitudinal axis of the elongate body 2212. A biasing elementsuch as a wire or push rod extending through elongate body 2212 canadjust the configuration of the delivery device 2200. If the biasingelement is a wire, the wire can be pulled to move the deployed section2230 into the arcuate shape. Alternatively, a sleeve 2210 can be sliddistally over the distal section 1230 to cover the deployed section 2230and constrain it in a straightened configuration during delivery. Whenthe sleeve is removed the deployed section 2230 will resiliently returnto the arcuate shape. In other embodiments, when a coolant is deliveredthrough the distal section 2230, the pressure of the coolant can causethe distal section 2230 to assume the curved shape (e.g., a spiralconfiguration, a coiled configuration, or a helical configuration).

FIG. 98 shows a delivery device 2300 with a visual indicator 2310 adisposed on shaft 2350. When an assembly 2320 is inflated in an airway,it may be difficult to see an electrode 2340, especially if theelectrode 2340 is between cartilaginous rings or if mucous is collectedaround the exterior of the balloon 2330. Thus, it may be difficult for aphysician to accurately position the electrode 2340. The visualindicator 2310 a is located proximally of the expandable element 2330and, thus, is viewable from a proximal position relative to theexpandable element. The visual indicator 2310 a corresponds to theposition of the electrode 2340. In some embodiments, including theillustrated embodiment, the electrode 2340 is positioned generallyradially outward and axially offset of the visual indicator 2310 a, asshown in FIG. 100. The electrode 2340 of FIG. 100 has an arc length thatis generally equal to an arc length of the visual indicator 2310 a.Based on the location of the visual indicator 2310 a, the physician candetermine the approximate location of the electrode ends 2352, 2354.This makes it easier for the physician to rotate and accurately positionthe electrode 2340.

The visual indicator or marking 2310 a can be colored, reflective, orotherwise readily visible through a bronchoscope. In some embodiments,the visual indicator 2310 a can be a longitudinally-extending stripe ormark. In other embodiments, the visual indicator 2310 a can be one ormore light sources. If the ablation assembly 2320 includes a pluralityof electrodes, different visual indicators can correspond to thepositions of different electrodes. Visual indicators can be located onthe elongate shaft 2350, the balloon 2330, electrode 2340, or othersuitable location.

FIG. 100 shows visual indicators positioned about the elongate shaft2350. Each of the visual indicators 2310 a, 2310 b, 2310 c, 2310 d(collectively “2310”) can be a different color. The user can positionthe ablation assembly 2320 using the visual indicators 2310. In otherembodiments, the proximal end of the balloon 2330 has visual indicators.

FIG. 101 shows a catheter 2400 positioned in a delivery apparatus 2410.An elongate body 2420 extends through a working lumen 2430. An opticalelement 2440 can be used to view and position the ablation assembly2450. A balloon 2460 can be transparent or semi-transparent.

The delivery apparatus 2410 is a bronchoscope with camera optics 2440. Adistal end 2470 of the camera optics 2440 is optically coupled to theballoon wall. The distal end 2470 can be pressed against the conformableballoon's proximal surface to provide optical coupling. During use, theuser may view the electrode or other components or anatomical featuresthrough the wall of the balloon and the fluid within the balloon.

In other embodiments, the delivery apparatus 2410 can be a sheath withfiber optics 2440 having lenses, light sources, cameras, or the like. Incertain embodiments, the optical element 2440 is integrated or coupledto the balloon 2460. This prevents mucous or other unwanted substancesfrom obscuring the user's view. The balloon geometry, specifically theangle of the proximal balloon wall, may be selected to optimize opticalcoupling with the camera optics 2440. The proximal balloon wall can havea section which can be aligned with the camera optics 2440 and which issubstantially flat, smooth, transparent, and which is parallel to theplane of the distal end 2470 of the camera optics 2440, preferably insome embodiments being disposed at an angle of about 75 degrees to about105 degrees relative to the longitudinal axis of the elongate body 2420.The material of the proximal balloon wall may be selected to optimizevisibility and transparency, e.g. with a refractive index which iscompatible with the camera optics 2440 and/or fluid within the balloon.

FIG. 102 shows an ablation assembly 2510 including an elongate shaft2530, a balloon 2540, and a displaceable energy emitter assembly 2550.The ablation assembly 2510, in a generally straight configuration, canbe moved out of a delivery apparatus 2500 to assume a curvedconfiguration, illustrated with an arc length of about 180 degrees. Anenergy emitter assembly 2550 can be biased to assume the preset spiralor curved shape. When it passes out of the working lumen 2520, it canassume the delivery configuration. Alternatively, the energy emitterassembly 2550 through which coolant can be delivered can be formed of ashape memory material.

As shown in FIG. 104, the balloon 2540 extends distally past a tip 2570.The inflated balloon 2540 is received by a curved section 2560 of theenergy emitter assembly 2510 such that an electrode 2571 is positionedalong the outside of the balloon 2540. The electrode 2571 can be cooledby the balloon 2540. Additionally or alternatively, the energy emitterassembly 2550 can have a cooling channel through which a coolant flows.In some embodiments, the energy emitter 2550 can be similar to theembodiments shown in FIGS. 54-57 that provide counter flows. In yetother embodiments, ports, vents, or other features can be incorporatedinto the energy emitter assembly 2550 to provide direct cooling of thetissue.

FIGS. 105 and 105A show an ablation assembly 2600 that includes acollapsible electrode 2614 carried on a conduit or tubular member 2618.The electrode 2614 can be a coating, thin foil, film, or otherelectrically conductive material. Different types of coating, plating,or other fabrication techniques can be used to form the electrode 2614.In other embodiments, the electrode 2614 can be coupled to an interiorsurface 2620 of the tubular member 2618. This prevents direct electrodecontact with tissue or bodily fluids.

FIGS. 106-108 show the collapsing process. FIG. 106 shows a balloon 2630in a partially collapsed configuration. The conduit 2618 holds theelectrode 2614 in a deployed configuration.

FIG. 107 shows the balloon 2630 in a fully collapsed configuration andthe energy emitter assembly 2634 in a collapsed configuration. Theradially collapsed electrode 2614 assumes a relatively small profile. Tofacilitate the collapsing process, a vacuum can be drawn. As shown inFIG. 108, the electrode 2614 can lay against the elongate body 2640 andthe balloon 2630 to assume a relatively low-profile position.

To inflate the ablation assembly 2600, a fluid can flow through andinflate the conduit 2618. An internal throttle valve can control therelative pressure between the conduit 2618 and the balloon 2630. FIG.106 shows the partially inflated balloon 2630. The fluid continues tofill the balloon 2630 until the balloon 2630 is fully deployed. Thus,the conduit 2618 can be fully inflated before completing inflation ofthe balloon 2630. Other types of inflation processes can also be used.

FIG. 109 shows an ablation assembly 2700 that includes an expandablebasket 2709 with displaceable electrode arms 2710 a, 2710 b, 2710 c,2710 d, 2710 e (collectively “2710”). The electrode arms 2710 arecircumferentially spaced about an expandable element 2720, illustratedas an inflatable balloon. The arms 2710 extend distally from an elongateshaft 2730. Each arm 2710 carries an electrode element 2740 a, 2740 b,2740 c, 2740 d, 2740 e (collectively “2740”). The arms 2710, which maybe a conductive shape memory material such as Nitinol, are resilientlybiased outwardly such that when extended distally from elongate shaft2730 they return to a radially expanded configuration as shown in FIG.110. Expandable element 2720 may be expanded to urge the arms 2710against the airway wall. Further a coolant may be circulated throughexpandable element 2720 to cool electrodes 2740 a-e and the tissueadjacent thereto.

FIG. 112 shows the elongate arm 2710 a with an insulator 2746 asurrounding an electrical conductor 2748 a. The electrical conductor2748 a provides electrical communication between the electrode 2740 aand the elongate shaft 2730. The electrical conductor may be aconductive metallic material used to form the arms 2710 themselves, suchas Nitinol.

FIG. 113 shows the electrodes 2740 a-e circumferentially spaced apartabout the periphery of the expandable element 2720. The illustratedembodiment includes five electrodes. A higher or lower number ofelectrodes can be used based on the number of treatment sites. In otherembodiments, a plurality of spaced apart electrodes can be positionedalong each of the elongate arms. The electrodes can be activatedsequentially or concurrently. In some embodiments, the electrodes can beoperated in monopolar mode at the same time. Alternatively, the variouspairs of plurality of electrodes can be operated in a bipolar mode. Awide range of different modes of operation can be used.

A delivery conduit 2754 of FIG. 113 delivers a coolant, represented byarrows, radially outward towards each electrode 2740. The coolant cancirculate in the balloon 2720.

FIGS. 114-116 show an ablation assembly 2800 including an expandableelement 2810 and a deployable energy emitter assembly 2820. The energyemitter assembly 2820 can be expanded to deploy a zig-zag or wave-shapedelectrode 2830. The deployed electrode 2830 extends between ends of apair of arms 2834 a, 2834 b. The illustrated electrode 2830 has a zigzagconfiguration, but other configurations are also possible.

To position the electrode 2830 near tissue, the expandable element 2810can be inflated to move the arms 2834 a, 2834 b outwardly. In someembodiments, the arms 2834 a, 2834 b are self-expanding. As the ablationassembly 2800 moves out of a working lumen of a delivery assembly, thearms 2834 a, 2834 b can assume an expanded configuration. In otherembodiments, the arm 2834 a, 2834 b are made of a shape memory materialand can be activated to assume the expanded configuration. The armsthemselves may be made of a conductive material such as Nitinol toconduct energy to the electrode 2830.

FIG. 117 shows a delivery device 2090 that includes a deployable basket2910. The deployable basket 2910 has an elongate shape and includes aplurality of elongated arms or struts carrying electrodes 2912. In otherembodiments, the basket 2910 can be generally spherical, ovoid, or canhave any other suitable configuration. Advantageously, air can passthrough the basket 2910 to maintain ventilation. The plurality of strutscan include passageways through which coolant flows, one or more valves(e.g., throttles, Joule-Thomson throttles, or the like). In someembodiments, cryogenic fluids or refrigerant(s) can be delivered throughthe struts (illustrated with five struts) for enhanced cooling. Theembodiments shown in FIGS. 54 and 57 can be incorporated into thestruts. In some embodiments, the elements 2912 can be in the form ofenergy emitting assemblies comprising electrodes and internal throttlevalves.

FIG. 118 shows the basket 2910 in a partially expanded configuration.The electrodes 2912 are moved radially outward as the basket expands.FIG. 119 shows the basket 29 under the fully expanded configuration. Apivot or joint 2914 of FIG. 119 can provide rotation of the basket 2910with respect to an elongate shaft 2918. This allows for flexibility whenplacing the basket 2910 along highly curved lumens. The pivot 2914 canbe formed by an articulating joint, a flexible member, a hinge, or othersuitable feature for providing relatively large amount of rotation.

The delivery devices disclosed herein can treat the digestive system,nervous system, vascular system, or other systems. For example, theelongate assemblies, intra-luminal catheters, and delivery devicesdisclosed herein can be delivered through blood vessels to treat thevascular system. The treatment systems and its components disclosedherein can used as an adjunct during another medical procedure, such asminimally invasive procedures, open procedures, semi-open procedures, orother surgical procedures (e.g., lung volume reduction surgery) thatprovide access to a desired target site. Various surgical procedures onthe chest may provide access to lung tissue. Access techniques andprocedures used to provide access to a target region can be performed bya surgeon and/or a robotic system. Those skilled in the art recognizethat there are many different ways that a target region can be accessed.

The delivery devices disclosed herein can be used with guidewires,delivery sheaths, optical instruments, introducers, trocars, biopsyneedles, or other suitable medical equipment. If the target treatmentsite is at a distant location in the patient (e.g., a treatment sitenear the lung root 24 of FIG. 1), a wide range of instruments andtechniques can be used to access the site. The flexible elongatedassemblies can be easily positioned within the patient using, forexample, steerable delivery devices, such as endoscopes andbronchoscopes, as discussed above.

Semi-rigid or rigid elongated assemblies can be delivered using trocars,access ports, rigid delivery sheaths using semi-open procedures, openprocedures, or other delivery tools/procedures that provide a somewhatstraight delivery path. Advantageously, the semi-rigid or rigidelongated assemblies can be sufficiently rigid to access and treatremote tissue, such as the vagus nerve, nerve branches, nerve fibers,and/or nerve trunks along the airways, without delivering the elongatedassemblies through the airways. The embodiments and techniques disclosedherein can be used with other procedures, such as bronchialthermoplasty.

Unless the context requires otherwise, throughout the specification andclaims which follow, the word “comprise” and variations thereof, such as“comprises” and “comprising” are to be construed in an open, inclusivesense, that is, as “including but not limited to.”

The various embodiments described above can be combined to providefurther embodiments. These and other changes can be made to theembodiments in light of the above-detailed description. The embodiments,features, systems, devices, materials, methods and techniques describedherein may, in some embodiments, be similar to any one or more of theembodiments, features, systems, devices, materials, methods andtechniques described in of application Ser. No. 12/463,304 filed on May8, 2009; U.S. Provisional Patent Application No. 61/255,367 filed Oct.27, 2009; and U.S. Provisional Patent Application No. 61/260,348 filedNov. 11, 2009. Each of these applications is incorporated herein byreference in its entirety. In addition, the embodiments, features,systems, devices, materials, methods and techniques described hereinmay, in certain embodiments, be applied to or used in connection withany one or more of the embodiments, features, systems, devices,materials, methods and techniques disclosed in the above-mentioned U.S.patent application Ser. No. 12/463,304. For example, the apparatuses ofdisclosed in U.S. patent application Ser. No. 12/463,304 may incorporatethe electrodes or other features disclosed herein.

In addition, the embodiments, features, systems, delivery devices,materials, methods and techniques described herein may, in certainembodiments, be applied to or used in connection with any one or more ofthe embodiments, features, systems, devices, materials, methods andtechniques disclosed in the above-mentioned of application Ser. No.12/463,304 filed on May 8, 2009; U.S. Provisional Patent Application No.61/255,367 filed Oct. 27, 2009; and U.S. Provisional Patent ApplicationNo. 61/260,348 filed Nov. 11, 2009.

In general, in the following claims, the terms used should not beconstrued to limit the claims to the specific embodiments disclosed inthe specification and the claims, but should be construed to include allpossible embodiments along with the full scope of equivalents to whichsuch claims are entitled. Accordingly, the claims are not limited by thedisclosure.

What is claimed is:
 1. A pulmonary treatment apparatus, comprising: an elongated shaft having proximal and distal ends, an inflow lumen and an outflow lumen extending between the proximal and distal ends; an ablation assembly positionable in an airway of a subject and coupled to the distal end of the shaft, the ablation assembly being fluidly coupled to the inflow lumen and the outflow lumen and including an energy emitter movable from a delivery configuration in which the energy emitter is positionable in a channel having a diameter of less than 6 mm to a deployed configuration in which the energy emitter engages a surface of the airway wall; a source of energy coupled to the energy emitter and configured to deliver energy thereto such that a lesion is created in target tissue spaced radially outward from the surface of the airway wall; and a cooling system fluidly coupled to the inflow lumen and configured to deliver a coolant to the ablation assembly so as to cool the surface of the airway wall sufficiently that airway tissue disposed between the energy emitter and the target tissue is not permanently damaged, wherein the energy emitter is configured to create the lesion that extends around the circumference of the airway without repositioning the energy emitter.
 2. The pulmonary treatment apparatus of claim 1, wherein the energy emitter comprises a single long electrode.
 3. The pulmonary treatment apparatus of claim 1, wherein the energy emitter comprises a plurality of circumferentially spaced apart electrodes.
 4. The pulmonary treatment apparatus of claim 3, wherein the electrodes are spaced between 45 and 210 degrees apart.
 5. The pulmonary treatment apparatus of claim 3, wherein the electrodes are spaced 45 degrees apart.
 6. The pulmonary treatment apparatus of claim 3, wherein the electrodes are spaced 90 degrees apart.
 7. The pulmonary treatment apparatus of claim 3, wherein the electrodes are spaced 180 degrees apart.
 8. The pulmonary treatment apparatus of claim 3, wherein the plurality includes three electrodes.
 9. The pulmonary treatment apparatus of claim 8, wherein the three electrodes are spaced about 60 degrees apart.
 10. The pulmonary treatment apparatus of claim 1, wherein the energy emitter has a helical configuration.
 11. The pulmonary treatment apparatus of claim 1, wherein the energy emitter comprises a pair of bipolar electrodes.
 12. The pulmonary treatment apparatus of claim 1, wherein the energy emitter comprises a plurality of axially and circumferentially spaced-apart electrodes.
 13. The pulmonary treatment apparatus of claim 1, wherein the energy emitter comprises a first portion positionable in a first intercartilagenous space and a second portion positionable in a second intercartilagenous space when the first electrode is positioned in the first intercartilagenous space.
 14. The pulmonary treatment apparatus of claim 13, wherein the first portion comprises a first electrode and the second portion comprises a second electrode spaced apart from the first electrode.
 15. The pulmonary treatment apparatus of claim 1, wherein the energy emitter assembly is configured to deliver RF energy to the airway wall.
 16. The pulmonary treatment apparatus of claim 1, wherein the energy emitter assembly is configured to deliver microwave energy to the airway wall.
 17. The pulmonary treatment apparatus of claim 1, wherein the energy emitter assembly is configured to deliver ultrasound energy to the airway wall.
 18. The pulmonary treatment apparatus of claim 1, wherein the ablation assembly comprises an expandable member movable from a collapsed configuration to an expanded configuration.
 19. The pulmonary treatment apparatus of claim 18, wherein the energy emitter is movable from the delivery configuration to the deployed configuration by the expandable member.
 20. The pulmonary treatment apparatus of claim 18, wherein the expandable member is configured to engage and cool airway tissue adjacent to the surface of the airway wall engaged by the energy emitter.
 21. The pulmonary treatment apparatus of claim 1, wherein the energy emitter assembly includes an electrode coupled to a fluid delivery conduit.
 22. The pulmonary treatment apparatus of claim 22, wherein the electrode is a collapsible electrode.
 23. The pulmonary treatment apparatus of claim 1, wherein the energy emitter assembly includes an electrode comprised of a foil, film or coating.
 24. A pulmonary treatment apparatus, comprising: an elongated shaft having proximal and distal ends, an inflow lumen and an outflow lumen extending between the proximal and distal ends; an ablation assembly positionable in an airway of a subject and coupled to the distal end of the shaft, the ablation assembly being fluidly coupled to the inflow lumen and the outflow lumen and including an energy emitter movable from a delivery configuration in which the energy emitter is positionable in a channel having a diameter of less than about 6 mm to a deployed configuration in which an energy emitting surface of the energy emitter engages a surface of the airway wall; a source of energy coupled to the energy emitter and configured to deliver energy thereto such that a lesion is created in target tissue spaced radially outward from the surface of the airway wall; and a cooling system fluidly coupled to the inflow lumen and configured to deliver a coolant to the ablation assembly so as to cool the surface of the airway wall sufficiently that airway tissue disposed between the energy emitter and the target tissue is not permanently damaged, wherein the ablation assembly is configured to extend around an arc at least about 180 degrees in length in the deployed configuration.
 25. The pulmonary treatment apparatus of claim 24, wherein the energy emitter is configured to create a lesion extending around an entire airway circumference without repositioning the energy emitter.
 26. The pulmonary treatment apparatus of claim 24, wherein the energy emitter comprises first and second portions circumferentially spaced from each other by about 45 to about 210 degrees.
 27. The pulmonary treatment apparatus of claim 26, wherein the first and second portions are circumferentially spaced about 90 degrees apart.
 28. The pulmonary treatment apparatus of claim 26, wherein the first and second portions are circumferentially spaced about 180 degrees apart.
 29. The pulmonary treatment apparatus of claim 24, wherein the energy emitter comprises a single electrode.
 30. The pulmonary treatment apparatus of claim 24, wherein the energy emitter comprises a plurality of discrete electrodes. 